AIM:To assess the activation of platelets and their phagocytic activity in the course of gastric cancer.METHODS:Forty-three gastric cancer patients were recruited to the study.The patients were divided into 3 groups d...AIM:To assess the activation of platelets and their phagocytic activity in the course of gastric cancer.METHODS:Forty-three gastric cancer patients were recruited to the study.The patients were divided into 3 groups depending on tumor stage.Group E included 6 patients with early gastric cancer;group A 18 patients with locally advanced cancer;and group M-19 with metastatic cancer.The investigations were performed twice,prior to surgery and 12-14 d afterwards.RESULTS:The platelet count and the level of soluble platelet selectin(sP-selectin) were found to increase with the disease progression.The level of sP-selectin was lowest in early cancer and was observed to increase after surgery in all the study patients.Irrespective of tumor stage,a statistically significant decrease was noted in the percentage of phagocytizing platelets and in the phagocytic index in gastric cancer patients as compared to healthy subjects.Despite increasedplatelet count and stimulation of thrombocytopoiesis,the phagocytic functions of blood platelets were markedly impaired.Tumor development seems to impair metabolic processes.CONCLUSION:A decreasing phagocytic activity can promote both inflammatory processes and cancer growth.展开更多
AIM: To assess the activation of platelets and their phagocytic activity in the course of gastric cancer. METHODS: Forty-three gastric cancer patients were recruited to the study. The patients were divided into 3 grou...AIM: To assess the activation of platelets and their phagocytic activity in the course of gastric cancer. METHODS: Forty-three gastric cancer patients were recruited to the study. The patients were divided into 3 groups depending on tumor stage. Group E included 6 patients with early gastric cancer; group A included 18 patients with locally advanced cancer; and group M included 19 patients with metastatic cancer. The investigations were performed twice, prior to surgery and 12-14 d afterwards. RESULTS: The platelet count and the level of sP-selectin were found to increase with the disease progression. The level of sP-selectin was lowest in early cancer and was observed to increase after surgery in all the study patients. Irrespective of tumor stage, a statistically significant decrease was noted in the percentage of phagocytizing platelets and in the phagocytic index in gastric cancer patients as compared to healthy subjects. Despite increased platelet count and stimulation of thrombocytopoiesis, the phagocytic functions of blood platelets were markedly impaired. Tumor development seems to impair metabolic processes. CONCLUSION: A decreasing phagocytic activity can promote both inflammatory processes and cancer growth.展开更多
The defense system of teleost fish organized on innate and adaptive immunity protects them against a wide variety of pathogenic microorganisms in the aquatic environment.Phagocytosis is one of the most effective defen...The defense system of teleost fish organized on innate and adaptive immunity protects them against a wide variety of pathogenic microorganisms in the aquatic environment.Phagocytosis is one of the most effective defense strategies against microbial challenge mainly performed by classical‘professional’phagocytes(including monocytes,macrophages and granulocytes).They contain,kill and process the internalized pathogens for antigen presentation by providing antigenic ligands to initiate activation and clonal expansion of T and B cells,which bridge the innate and adaptive immunity.The discovery of phagocytic B cells in teleost fish has broken the paradigm that primary vertebrate B cells are lack of phagocytosis of particulates,as well as led to the investigation of phagocytic activity of mammalian B-1 B cells.The active phagocytic,microbicidal capabilities and antigen presentation in teleost phagocytic B cell have demonstrated to be similar as professional phagocytes,providing a potential impact on development of new vaccination strategies to prevent and control infectious diseases.In this review,we aim to address current progress on the antimicrobial role of phagocytic B cells in teleost fish by comparing it with other professional phagocytes and mammalian B-1 B cells,and provide the application prospect of phagocytic B cells in developing vaccines as well as the prevention of fish diseases.展开更多
To the Editor:A 20-year-old man who developed hemophagocytic lymphohistiocytosis(HLH)was treated with methylprednisolone combined with etoposide(VP-16)for 24 weeks.One month after treatment completion,HLH recurred.The...To the Editor:A 20-year-old man who developed hemophagocytic lymphohistiocytosis(HLH)was treated with methylprednisolone combined with etoposide(VP-16)for 24 weeks.One month after treatment completion,HLH recurred.The patient visited the Hematology Department of the Beijing Friendship Hospital and was diagnosed with primary HLH with PRF1 fusion gene mutation.展开更多
To the Editor:Hemophagocytic lymphohistiocytosis(HLH)is a severe or even fatal inflammatory condition.Malignant HLH(M-HLH)is one of the most common types of secondary HLH(sHLH),especially in adults.HLH can occur eithe...To the Editor:Hemophagocytic lymphohistiocytosis(HLH)is a severe or even fatal inflammatory condition.Malignant HLH(M-HLH)is one of the most common types of secondary HLH(sHLH),especially in adults.HLH can occur either as the initial manifestation of malignant disease(here referred to as“malignancy-triggered HLH”)or in the setting of iatrogenic immuno-suppression from chemotherapy(“HLH during chemotherapy”or Ch-HLH).展开更多
Objective:To evaluated the immunomodulatory effect of BRP-4,an acidic polysaccharide from Basella rubra(B.rubra) L on the macrophage activity.Methods:Phagocytic activity was determined by the ingestion of Latex Beads-...Objective:To evaluated the immunomodulatory effect of BRP-4,an acidic polysaccharide from Basella rubra(B.rubra) L on the macrophage activity.Methods:Phagocytic activity was determined by the ingestion of Latex Beads-Rabbit IgC-FITC using the fluorescent microscopy and flow cytometry analysis and nitric oxide production was measured using Griess reaction assay.Results:An enhanced production of NO was observed at 10 and 100 μg/mL of BRP-4.The phagocytic activity of macrophage was enhanced in BRP-4 treated RAW264.7 cells.BRP-4combined with concanavalin A(Con A) provided obvious promotion and strengthening of the proliferation of the splenocytes.Conclusions:BRP-4,polysaccharide isolated from B.rubra,is suggested to activate macrophage function and stimulate splenocyte proliferation.The strong immunomodulatory activity of BRP-4 confirmed its good potential as an immunotherapeutic adjuvant.展开更多
Objective:To explore the immunomodulatory properties of 80% ethanol extract and butanol fraction of Gentiana olivieri(G. olivieri) Griseb on Balb/C mice.Methods:The study was performed with basic models of immunomodul...Objective:To explore the immunomodulatory properties of 80% ethanol extract and butanol fraction of Gentiana olivieri(G. olivieri) Griseb on Balb/C mice.Methods:The study was performed with basic models of immunomodulation such as the humoral antibody response(hemoglutination antibody titres), cell mediated immune response(delayed type hypersensitivity and in vivocarbon clearance or phagocytosis). Ethanol(80%) extract of flowering aerial parts of G.olivieriand its butanol fraction were administered p.o.(orally) to the mice. Levamisole, 2.5 mg/kg was used as standard drug.Results:There was a potentiation of immune response to sheep red blood cells by cellular and humoral mediated mechanisms comparable to levamisole(2.5 mg/kg) by both 80% ethanol extract and the butanol fraction at doses of 50-200 mg/kg in male Balb/C mice. Both significantly(P<0.01) potentiated the humoral immune response in cyclophosphamide(250 mg/kg)immunosupressed mice at 100 and 200 mg/kg of each extract and fraction as compared to control.The potentiation of delayed type hypersensitivity response was statistically significant(P<0.01) at200 mg/kg of ethanol extract and 100, 200 mg/kg of butanol fraction as compared to control. The phagocytosis was significant at 200 mg/kg with butanol fraction ofG. olivieri.Conclusions:The results reveal the immunostimulant effects of plantG. olivieriin mice by acting through cellular and humoral immunity in experimental models of immunity in mice. Butanol fraction is the most effective at a dose level of 200 mg/kg.展开更多
The aim of this work was a study of the functional activity of neutrophils and peripheral blood monocytes in rats with the transplanted Walker carcinosarcoma as potential predictors of the sensitivity of this tumor to...The aim of this work was a study of the functional activity of neutrophils and peripheral blood monocytes in rats with the transplanted Walker carcinosarcoma as potential predictors of the sensitivity of this tumor to doxorubicin treatment. This study provides an evidence that such indices of the functional activity of circulating phagocytes of the tumor-bearing rats as the quantity and the phagocytosis intensity of monocytes, as well as the intensity of ROS production by monocytes and neutrophils, may reflect the degree of sensitivity of the tumor to doxorubicin. So it was shown that the growth of the resistant tumor caused a significant increase of the number of circulating phagocytic cells and the intensity of phagocytosis by more than 100% (p < 0.001) compared with the corresponding indices of intact rats and rats with the parental variant of the tumor. The ability of blood mono-cytes and neutrophils of rats with a resistant tumor to produce ROS was also significantly different from that in intact rats and animals with the parental carcinosarcoma variant. The predictive value of these indices is especially important in the dynamic monitoring of the development of tumor drug resistance during long-term cancer chemotherapy. Considering the standard 2 - 3 week interval between the courses of cancer therapy and the short lifetime of circulating phagocytes, an assessment of the indices of their functional activity before each subsequent course can be considered as a pretreatment assessment. Meanwhile, further studies are needed to determine the spectrum of malignant neoplasms for which the degree of tumor drug resistance correlates with the functional activity of circulating phagocytes.展开更多
Hot water extract from the edible Brazilian mushroom, Agaricus Blazei Murill (ABM), is used for both traditional and alternative medicine. ABM is reported to stimulate anti-tumor, anti-infection, and immune activity. ...Hot water extract from the edible Brazilian mushroom, Agaricus Blazei Murill (ABM), is used for both traditional and alternative medicine. ABM is reported to stimulate anti-tumor, anti-infection, and immune activity. However, there are few reports of how ABM affects neutrophils. Therefore, in this study, we examined the effect of hot water ABM extract on neutrophil migration, phagocytosis, and reactive oxygen species production using neutrophils from guinea pig. Migratory direction and velocity as indicators of chemotactic activity of neutrophils were significantly (p 0.001) increased at concentration of 50 and 100 mg/ml in ABM extract compared with control. Phagocytic activity of neutrophil was significantly (p 0.01) increased at concentration of 5 mg/ml in ABM extract compared with control. Production of reactive oxygen species (ROS: H2O2 or ) by neutrophils was significantly (p 0.01) increased at concentration of 5 mg/ml in ABM extract compared with control. These results suggest that enhancement in neutrophil chemotactic activity, phagocytic activity and ROS production are mechanisms by which ABM extract inhibits bacterial infection in the skin and dermatitis.展开更多
Coxiella burnetii is an obligate intracellular pathogen and the causative agent of Q fever.In this brief review,we describe how recently described mechanisms help our understanding of C.burnetii invasion and its survi...Coxiella burnetii is an obligate intracellular pathogen and the causative agent of Q fever.In this brief review,we describe how recently described mechanisms help our understanding of C.burnetii invasion and its survival in the host cell by the formation of a replicative niche:the Coxiella-containing vacuole.We describe the actin-associated proteins involved in the internalization of C.burnetii,and we discuss the contribution of diverse degradation pathways of the cell during the formation and stabilization of the Coxiella-containing vacuole.展开更多
This study was to explore the immunity-promoting activity of porcine placenta as a potential raw material for functional foods.Porcine placenta was subjected to the analysis for its bioactive substances,and their immu...This study was to explore the immunity-promoting activity of porcine placenta as a potential raw material for functional foods.Porcine placenta was subjected to the analysis for its bioactive substances,and their immunity-promoting activity was determined in mice supplemented with porcine placenta extract(PPE)and freeze-dried porcine placenta powder at high(PPH)and low(PPL)dosage.Results showed that porcine placenta contained placental peptides and 15 free amino acids,and the amounts of estrogen and progesterone in products developed from porcine placenta were within the limit of national standard.Mice model experiment revealed that compared with the control,the PPH treatment significantly improved the spleen index(P<0.05)by increasing the phagocytic rate of macrophages from 20%to 60%and the conversion rate of T lymphocytes from 8%to 60%.The q PCR analysis disclosed that the porcine placenta powder enhanced mice immunity via promoting the expression of Th1 cytokines of interleukin-2(IL-2)and IFN-γ,especially the former,by almost 8 times in the spleens of male mice,while inhibited Th2 cytokines of IL-4 and IL-10.This investigation has provided a reference for the development of porcine placenta as a raw material applied in functional foods to improve human immunity.展开更多
Alveolar macrophages (AM) are known to play an essential role in lung defense through their ability to remove the foreign matters reaching the lung alveoli. Cigarette smoke (CS) is a critical risk factor for many lung...Alveolar macrophages (AM) are known to play an essential role in lung defense through their ability to remove the foreign matters reaching the lung alveoli. Cigarette smoke (CS) is a critical risk factor for many lung diseases. CS is inhaled into the lung by respiretion and affects AM. It has been previously reported that CS induces inhibition of cytokine production, cell surface receptor expression and antigen presentation in AM. However, the relationship of immune suppression and DNA damage caused by CS in AM is still unclear. Therefore, in this study, we investigated AM immune function and DNA damage in CS-exposed mice. Mice were exposed to CS of 20 cigarettes/day during 10 days using a HambrugⅡsmoking machine. After exposure, AM were obtained by bronchoalveolar lavage. The number of AM was significantly increased in CS-exposed mice compared with non-CS-exposed mice. Phagocytic activity of AM was significantly inhibited by CS exposure. Percentage of CD11b-, CD14-, Toll-like receptor (TLR)2- or TLR4-positive cells was significantly decreased in CS-exposed mice compared with non-CS-exposed mice. Interleukin-1β mRNA expression in lipopolysaccharide-stimulated AM was significantly inhibited by CS exposure. Intracellular reactive oxygen species (ROS) (, H2O2) production of AM was significantly increased, and DNA damage was induced by CS exposure. These results suggest that impaired immune functions by CS exposure may be related to DNA damage via excessive ROS induced by CS. These alterations of AM caused by CS could be associated with infection and development of pulmonary diseases.展开更多
The objective of the current work is to investigate the possible beneficial effects of forced feeding of fenugreek to rabbit does on their milk composition, milk yield, anemia screening parameters, immunity and the gr...The objective of the current work is to investigate the possible beneficial effects of forced feeding of fenugreek to rabbit does on their milk composition, milk yield, anemia screening parameters, immunity and the growth performance of bunnies. Twenty white New Zealand female rabbits were randomly assigned into 5 groups: normal control and 4 treated groups (vehicle (molasses), fenugreek powdered seeds + molasses, sprouted fenugreek + molasses, and fenugreek oil + molasses). All treated groups took the given doses orally for two days before parturition and 13 days after parturition for 2 successive pregnancies. Blood samples were collected from each doe on the 13<sup>th</sup> day of lactation for determination of hematological, biochemical and immunological parameters. Milk samples were taken for evaluation of milk composition. All rabbit does and their bunnies were weighed for calculation of the milk yield. The fenugreek seeds and oil administered groups (G<sup>3</sup> & G<sup>5</sup>) recorded the highest percent values of fat, protein, lactose, total solids and solid not fat contents of the rabbits’ milk in both 1st and 2nd lactation periods relative to other tested groups. At the beginning and mid of lactation periods, the milk yields recorded non-significant differences either between tested groups or between 1<sup>st</sup> and 2<sup>nd</sup> pregnancy in the same group. Whereas, at the end of lactation, germinated seeds (G<sup>4</sup>) and oil (G<sup>5</sup>) treated groups recorded significantly higher rates of milk yield relative to control and fenugreek seeds groups. Bunnies’ body weights suckling from dams of group III (G<sup>3</sup>) recorded the highest weights relative to other tested groups in both 1<sup>st</sup> and 2<sup>nd</sup> pregnancy. During the 1<sup>st</sup> lactation period, all experimental groups showed significant reduction of white blood cells, while, G<sup>3</sup> and G<sup>4</sup> recorded significant elevation during 2<sup>nd</sup> lactation period. Rabbits treated with fenugreek seeds powder (G<sup>3</sup>) showed a significant raise of phagocytic activity and phagocytic index. Fenugreek seeds group (G<sup>3</sup>) and germinated one (G<sup>4</sup>) showed significant red blood corpuscles and packed cell volume raise relative to other groups during both 1<sup>st</sup> and 2<sup>nd</sup> lactation periods.展开更多
Microglia, as the resident immune cells in the central nervous system, play important roles in regulating neuronal processes, such as neural excitability, synaptic activity, and apoptotic cell clearance. Growth factor...Microglia, as the resident immune cells in the central nervous system, play important roles in regulating neuronal processes, such as neural excitability, synaptic activity, and apoptotic cell clearance. Growth factors can activate multiple signaling pathways in central nervous system microglia and can regulate their immune effects, but whether growth factors can affect the morphological characteristics and ultrastructure of microglia has not been reported. After microinjecting 300 nL of a growth factor cocktail, including 10 μg/mL epidermal growth factor, 10 μg/mL basic fibroblast growth factor, 10 μg/mL hepatocyte growth factor and 10 μg/mL insulin-like growth factor into adult rat cortex, we found that the number of IBA1-positive microglia around the injection area increased significantly, indicating local activation of microglia. All CD68-positive labeling co-localized with IBA1 in microglia. Cell bodies and protrusions of CD68-positive cells were strongly attached to or were engulfing neurons. Characteristic huge phagosomes were observed in activated phagocytes by electron microscopy. The phagosomes generally included non-degraded neuronal protrusions and mitochondria, yet they contained no myelin membrane or remnants, which might indicate selective phagocytosis by the phagocytes. The remnant myelin sheath after phagocytosis still had regenerative ability and formed "myelin-like" structures around phagocytes. These results show that microinjection of a growth factor cocktail into the cerebral cortex of rodents can locally activate microglia and induce selective phagocytosis of neural structures by phagocytes. The study was approved by the Institute of Laboratory Animal Science, Beijing Institute of Basic Medical Sciences(approval No. IACUC-AMMS-2014-501) on June 30, 2014.展开更多
Background: Glucose is the main substrate for the generation of NADPH, the cofactor of the oxidative burst enzyme NADPH-oxidase of blood neutrophils. Changes in blood glucose are thus expected to modify the generation...Background: Glucose is the main substrate for the generation of NADPH, the cofactor of the oxidative burst enzyme NADPH-oxidase of blood neutrophils. Changes in blood glucose are thus expected to modify the generation of reactive oxygen species (ROS). The new blood ROS generation assay (BRGA) quantifies ROS changes induced by blood glucose concentrations as they are found in diabetes mellitus. Material and Methods: Citrated or EDTA blood of 6 healthy donors were analyzed in the BRGA: 10 μl sample in black polystyrene F-microwells (Brand 781608) were incubated in triplicate with 125 μl Hanks’ balanced salt solution, 40 μl 0 - 200 mM glucose in 0.9% NaCl (final added conc.: 0 - 41 mM;final basal glucose conc.: about4 mM), 10 μl5 mMluminol, and 10 μl zymosan A (final conc.: 1.9 μg/ml) in 0.9% NaCl. The plates were measured within 0 - 250 min (37℃) in a photons-multiplyer microtiter plate luminometer (LUmo) with an integration time of 1 s. Results: Up to about 30 min reaction time the mean ROS generation was 50% inhibited by about1 mMadded glucose (= approx. IC50). At ≥80 min reaction time (possibly necessary for full phosphorylation of glucose to glucose-6-phosphate (G6P), the substrate metabolized by G6P-dehydrogenase to generate NADPH, the cofactor of the NADPH-oxidase) the mean ROS generation approximately doubled at about1 mMadded glucose (= approx. SC200) in citrated blood. Discussion: Elevated glucose concentrations not only increase systemic thrombin generation, they can also diminish cellular fibrinolysis and increase systemic inflammation, resulting in a chronic pro-thrombotic state. The fascinating importance of NADPH-oxidases not only in phagocytes but also in the beta cells of pancreas points towards a new pathogenesis explication of diabetes mellitus type 1: whatever stimulus (e.g. a pancreas-tropic virus) could activate the beta cell’s autodestructive NADPH-oxidase.展开更多
Objective: To investigate the leishmanicidal effects of two antioxidants, caffeic acid and quercetin on Leishmania major(L.major) promastigotes in vitro, and their immunomodulatory effects on infected phagocytes deriv...Objective: To investigate the leishmanicidal effects of two antioxidants, caffeic acid and quercetin on Leishmania major(L.major) promastigotes in vitro, and their immunomodulatory effects on infected phagocytes derived from susceptible BALB/c mice.Methods: Caffeic acid and quercetin-induced cell death was examined by Pi-Hoechst double staining of L.major promastigotes and MTT assay, in the presence or absence of protease inhibitors in vitro.Caffeic acid or quercetin were administered subcutaneously to BALB/c mice infected with L.major promastigotes through a dorsal air pouch.Nitric oxide and superoxide anion production by phagocytes infiltrating the air pouch and the expression of inducible nitric oxide synthase(i NOS), tumor necrosis factor alpha(TNF-a) and nuclear factor kappa B in the air pouch membrane were therefore evaluated using appropriate methods.Results: Caffeic acid and quercetin displayed a dose-dependent cytotoxic effect against L.major promastigotes, and induced cell death via caspases-independent pathways.In vivo, L.major promastigotes inoculation into air pouch cavity of BALB/c mice leads to a sequential influx of neutrophils(hours), followed by macrophages(days).Results showed that L.major delayed apoptosis of infected neutrophils and macrophages by the cleavage of the nuclear factor kappa B p65^(RelA) subunit, and persisted by inhibiting TNF-a and i NOS expression and reactive oxygen species generation.Caffeic acid or quercetin restored reactive oxygen species production and TNF-a-induced i NOS activity, and abrogate apoptosis delay of infected phagocytes.Conclusions: The leishmanicidal effect of caffeic acid and quercetin on promastigotes and amastigotes, as well as reactivation of infected phagocytes apoptosis, suggested a potential therapeutic role against cutaneous leishmaniasis.展开更多
The mononuclear phagocyte system(MPS)consists of monocytes,dendritic cells and macrophages,which play vital roles in innate immune defense against cancer.Hepatocellular carcinoma(HCC)is a complex disease that is affec...The mononuclear phagocyte system(MPS)consists of monocytes,dendritic cells and macrophages,which play vital roles in innate immune defense against cancer.Hepatocellular carcinoma(HCC)is a complex disease that is affected or initiated by many factors,including chronic hepatitis B virus infection,hepatitis C virus infection,metabolic disorders or alcohol consumption.Liver function,tumor stage and the performance status of patients affect HCC clinical outcomes.Studies have shown that targeted treatment of tumor microenvironment disorders may improve the efficacy of HCC treatments.Cytokines derived from the innate immune response can regulate T-cell differentiation,thereby shaping adaptive immunity,which is associated with the prognosis of HCC.Therefore,it is important to elucidate the function of the MPS in the progression of HCC.In this review,we outline the impact of HCC on the MPS.We illustrate how HCC reshapes MPS cell phenotype remodeling and the production of associated cytokines and characterize the function and impairment of the MPS in HCC.展开更多
Until recently,microglia were mainly known as the resident phagocytes of the brain,i.e.the‘immunological warriors’of the brain.However,extensive knowledge is being accumulated about the functions of microglia beyond...Until recently,microglia were mainly known as the resident phagocytes of the brain,i.e.the‘immunological warriors’of the brain.However,extensive knowledge is being accumulated about the functions of microglia beyond immunity.Nowadays,it is well accepted that microglial cells are highly dynamic and responsive,and that they intervene in a dual manner in many developmental processes that shape the central nervous system,including neurogenesis,gliogenesis,spatial patterning,synaptic formation and elimination,and neural circuit establishment and maturation.The differentiation and the pool of precursor cells were also shown to be under microglia regulation via bidirectional communication.In this concise review,I discuss our recent work in microglia-Pax6+cell interactions in one of the circumventricular organs,the pineal gland.An analogy with the rest of the central nervous system is also presented.In addition,I briefly examine mechanisms of interaction between microglia and non-microglial cells in both health and disease.New avenues are also introduced,which may lead us to better comprehend the impact of microglia in physiological and pathological conditions.展开更多
The aim of this study is to evaluate the effect of moderate physical exercise and treatment time on the organism’s response to NSC631570. The sensitivity of circulating phagocytes to the drug at different times of da...The aim of this study is to evaluate the effect of moderate physical exercise and treatment time on the organism’s response to NSC631570. The sensitivity of circulating phagocytes to the drug at different times of day was estimated in in vitro experiments. NSC631570 was administered intravenously to healthy volunteers (eleven men, 23 ± 2 years) in a single therapeutic dose in an inpatient and an outpatient setting. Blood samples were obtained before the drug administration, 30 min after the drug injection and every fourth hour throughout the 24 hour period. Biochemical parameters were determined using the hematological analyzer. Flow cytometry was used to evaluate phagocyte metabolism. Treatment of circulating phagocytes with NSC631570 in vitro resulted in an increase in ROS production along with a decrease in their phagocytic activity, most expressed in the morning time. Drug injection to sedentary persons resulted in pro-inflammatory metabolic polarization of circulating phagocytes. Introduction of NSC631570 to active persons was accompanied by a significant increase in phagocyte endocytosis along with a decrease in the daily mean of ROS generation. Significant oscillation (but in the normal ranges) of urea, creatinine, alanine aminotransferase and aspartate aminotransferase after NSC631570 introduction in the outpatient setting was shown during the day. Physical activity interferes with immunomodulatory action of NSC631570 and abrogates pro-inflammatory shift of circulating phagocytes. Biochemical parameters of blood from patients treated with NSC631570 in the outpatient setting must be interpreted cautiously considering the effect of physical activity on some metabolic biomarkers.展开更多
The capacities of phagocytes of subpopulation P1 (F) and morula cells (MC) of holothurian Eupentacta fraudatrix to modulate apoptosis of each other as well as cytokine-dependent mechanisms and hormonal regulation of t...The capacities of phagocytes of subpopulation P1 (F) and morula cells (MC) of holothurian Eupentacta fraudatrix to modulate apoptosis of each other as well as cytokine-dependent mechanisms and hormonal regulation of these cells’s interaction were studied. The 18-h treatment of F with supernatants, obtained after centrifugation of MC preincubated for 3 h with phosphate buffered saline (PSB) at the temperature of 22℃?(SMC3) resulted in a significant growth of apoptosis level. A 30-min incubation of F with supernatants of MC, preincubated for 24 h (SMC24), on the contrary, reduced the apoptosis level and increased the level of interleukine-1α (IL-1α)-like substances, and 24-h incubation did not influence apoptosis and reduced level of IL-1α-like substances. Thus, proapoptotic effects of MC’s supernatants in F inversely depended on time of their preincubation with PSB and directly on time of incubation with F. Additionally, this effect was opposite to variations in the level of IL-1α-like substances. The level of apoptosis declined after 30 min of incubation but elevated after 24 h at the inverse treatment of MC with supernatant, obtained after preincubation of F during 24 h (SF24). The level of IL-1α-like substances dropped after 30 min and insignificantly decreased after 24 h. Hence, SF24 proapoptotic effect directly depended on time of incubation with MC and did not correspond to variations in the level of IL-1α-like substances. 100 μM dexamethasone stimulated apoptosis in F and MC in an inverse time-dependent manner during 24-h preincubation, and supernatants of cell suspensions obtained after such preincubations, stimulated apoptosis and reduced the IL-1α-like substances level in target cells at both types of interaction. IL-1α-like substances are?supposed to be mediators for MC’s effects in F, but not for F’s action on MC. In holothurians, steroid hormones apparently may participate in the regulation of the immune response and cell cooperation.展开更多
文摘AIM:To assess the activation of platelets and their phagocytic activity in the course of gastric cancer.METHODS:Forty-three gastric cancer patients were recruited to the study.The patients were divided into 3 groups depending on tumor stage.Group E included 6 patients with early gastric cancer;group A 18 patients with locally advanced cancer;and group M-19 with metastatic cancer.The investigations were performed twice,prior to surgery and 12-14 d afterwards.RESULTS:The platelet count and the level of soluble platelet selectin(sP-selectin) were found to increase with the disease progression.The level of sP-selectin was lowest in early cancer and was observed to increase after surgery in all the study patients.Irrespective of tumor stage,a statistically significant decrease was noted in the percentage of phagocytizing platelets and in the phagocytic index in gastric cancer patients as compared to healthy subjects.Despite increasedplatelet count and stimulation of thrombocytopoiesis,the phagocytic functions of blood platelets were markedly impaired.Tumor development seems to impair metabolic processes.CONCLUSION:A decreasing phagocytic activity can promote both inflammatory processes and cancer growth.
文摘AIM: To assess the activation of platelets and their phagocytic activity in the course of gastric cancer. METHODS: Forty-three gastric cancer patients were recruited to the study. The patients were divided into 3 groups depending on tumor stage. Group E included 6 patients with early gastric cancer; group A included 18 patients with locally advanced cancer; and group M included 19 patients with metastatic cancer. The investigations were performed twice, prior to surgery and 12-14 d afterwards. RESULTS: The platelet count and the level of sP-selectin were found to increase with the disease progression. The level of sP-selectin was lowest in early cancer and was observed to increase after surgery in all the study patients. Irrespective of tumor stage, a statistically significant decrease was noted in the percentage of phagocytizing platelets and in the phagocytic index in gastric cancer patients as compared to healthy subjects. Despite increased platelet count and stimulation of thrombocytopoiesis, the phagocytic functions of blood platelets were markedly impaired. Tumor development seems to impair metabolic processes. CONCLUSION: A decreasing phagocytic activity can promote both inflammatory processes and cancer growth.
基金supported by the National Natural Science Foundation of China(32102827,31972818,31528019)China Postdoctoral Science Foundation(2019M662959)+1 种基金Guangdong Basic and Applied Basic Research Foundation(2019A1515110987)Special fund for promoting economic development(for modern fishery development)of Guangdong Province(grant number 2019A4).
文摘The defense system of teleost fish organized on innate and adaptive immunity protects them against a wide variety of pathogenic microorganisms in the aquatic environment.Phagocytosis is one of the most effective defense strategies against microbial challenge mainly performed by classical‘professional’phagocytes(including monocytes,macrophages and granulocytes).They contain,kill and process the internalized pathogens for antigen presentation by providing antigenic ligands to initiate activation and clonal expansion of T and B cells,which bridge the innate and adaptive immunity.The discovery of phagocytic B cells in teleost fish has broken the paradigm that primary vertebrate B cells are lack of phagocytosis of particulates,as well as led to the investigation of phagocytic activity of mammalian B-1 B cells.The active phagocytic,microbicidal capabilities and antigen presentation in teleost phagocytic B cell have demonstrated to be similar as professional phagocytes,providing a potential impact on development of new vaccination strategies to prevent and control infectious diseases.In this review,we aim to address current progress on the antimicrobial role of phagocytic B cells in teleost fish by comparing it with other professional phagocytes and mammalian B-1 B cells,and provide the application prospect of phagocytic B cells in developing vaccines as well as the prevention of fish diseases.
基金supported by the National Natural Science Foundation of China(No.81871633)Beijing Natural Science Foundation(No.7181003).
文摘To the Editor:A 20-year-old man who developed hemophagocytic lymphohistiocytosis(HLH)was treated with methylprednisolone combined with etoposide(VP-16)for 24 weeks.One month after treatment completion,HLH recurred.The patient visited the Hematology Department of the Beijing Friendship Hospital and was diagnosed with primary HLH with PRF1 fusion gene mutation.
基金This work was supported by the National Natural Science Foundation of China(No.81871633).
文摘To the Editor:Hemophagocytic lymphohistiocytosis(HLH)is a severe or even fatal inflammatory condition.Malignant HLH(M-HLH)is one of the most common types of secondary HLH(sHLH),especially in adults.HLH can occur either as the initial manifestation of malignant disease(here referred to as“malignancy-triggered HLH”)or in the setting of iatrogenic immuno-suppression from chemotherapy(“HLH during chemotherapy”or Ch-HLH).
文摘Objective:To evaluated the immunomodulatory effect of BRP-4,an acidic polysaccharide from Basella rubra(B.rubra) L on the macrophage activity.Methods:Phagocytic activity was determined by the ingestion of Latex Beads-Rabbit IgC-FITC using the fluorescent microscopy and flow cytometry analysis and nitric oxide production was measured using Griess reaction assay.Results:An enhanced production of NO was observed at 10 and 100 μg/mL of BRP-4.The phagocytic activity of macrophage was enhanced in BRP-4 treated RAW264.7 cells.BRP-4combined with concanavalin A(Con A) provided obvious promotion and strengthening of the proliferation of the splenocytes.Conclusions:BRP-4,polysaccharide isolated from B.rubra,is suggested to activate macrophage function and stimulate splenocyte proliferation.The strong immunomodulatory activity of BRP-4 confirmed its good potential as an immunotherapeutic adjuvant.
基金financially supported by Goverment of India(grant No.SR/FT/LS-0083/2008)
文摘Objective:To explore the immunomodulatory properties of 80% ethanol extract and butanol fraction of Gentiana olivieri(G. olivieri) Griseb on Balb/C mice.Methods:The study was performed with basic models of immunomodulation such as the humoral antibody response(hemoglutination antibody titres), cell mediated immune response(delayed type hypersensitivity and in vivocarbon clearance or phagocytosis). Ethanol(80%) extract of flowering aerial parts of G.olivieriand its butanol fraction were administered p.o.(orally) to the mice. Levamisole, 2.5 mg/kg was used as standard drug.Results:There was a potentiation of immune response to sheep red blood cells by cellular and humoral mediated mechanisms comparable to levamisole(2.5 mg/kg) by both 80% ethanol extract and the butanol fraction at doses of 50-200 mg/kg in male Balb/C mice. Both significantly(P<0.01) potentiated the humoral immune response in cyclophosphamide(250 mg/kg)immunosupressed mice at 100 and 200 mg/kg of each extract and fraction as compared to control.The potentiation of delayed type hypersensitivity response was statistically significant(P<0.01) at200 mg/kg of ethanol extract and 100, 200 mg/kg of butanol fraction as compared to control. The phagocytosis was significant at 200 mg/kg with butanol fraction ofG. olivieri.Conclusions:The results reveal the immunostimulant effects of plantG. olivieriin mice by acting through cellular and humoral immunity in experimental models of immunity in mice. Butanol fraction is the most effective at a dose level of 200 mg/kg.
文摘The aim of this work was a study of the functional activity of neutrophils and peripheral blood monocytes in rats with the transplanted Walker carcinosarcoma as potential predictors of the sensitivity of this tumor to doxorubicin treatment. This study provides an evidence that such indices of the functional activity of circulating phagocytes of the tumor-bearing rats as the quantity and the phagocytosis intensity of monocytes, as well as the intensity of ROS production by monocytes and neutrophils, may reflect the degree of sensitivity of the tumor to doxorubicin. So it was shown that the growth of the resistant tumor caused a significant increase of the number of circulating phagocytic cells and the intensity of phagocytosis by more than 100% (p < 0.001) compared with the corresponding indices of intact rats and rats with the parental variant of the tumor. The ability of blood mono-cytes and neutrophils of rats with a resistant tumor to produce ROS was also significantly different from that in intact rats and animals with the parental carcinosarcoma variant. The predictive value of these indices is especially important in the dynamic monitoring of the development of tumor drug resistance during long-term cancer chemotherapy. Considering the standard 2 - 3 week interval between the courses of cancer therapy and the short lifetime of circulating phagocytes, an assessment of the indices of their functional activity before each subsequent course can be considered as a pretreatment assessment. Meanwhile, further studies are needed to determine the spectrum of malignant neoplasms for which the degree of tumor drug resistance correlates with the functional activity of circulating phagocytes.
文摘Hot water extract from the edible Brazilian mushroom, Agaricus Blazei Murill (ABM), is used for both traditional and alternative medicine. ABM is reported to stimulate anti-tumor, anti-infection, and immune activity. However, there are few reports of how ABM affects neutrophils. Therefore, in this study, we examined the effect of hot water ABM extract on neutrophil migration, phagocytosis, and reactive oxygen species production using neutrophils from guinea pig. Migratory direction and velocity as indicators of chemotactic activity of neutrophils were significantly (p 0.001) increased at concentration of 50 and 100 mg/ml in ABM extract compared with control. Phagocytic activity of neutrophil was significantly (p 0.01) increased at concentration of 5 mg/ml in ABM extract compared with control. Production of reactive oxygen species (ROS: H2O2 or ) by neutrophils was significantly (p 0.01) increased at concentration of 5 mg/ml in ABM extract compared with control. These results suggest that enhancement in neutrophil chemotactic activity, phagocytic activity and ROS production are mechanisms by which ABM extract inhibits bacterial infection in the skin and dermatitis.
基金supported by grants from Agencia Nacional de Promocion Cientifica y Tecnologica(PICT2012 no.2425)SECTyP-Universidad Nacional de Cuyo(06/J468)to W.B.
文摘Coxiella burnetii is an obligate intracellular pathogen and the causative agent of Q fever.In this brief review,we describe how recently described mechanisms help our understanding of C.burnetii invasion and its survival in the host cell by the formation of a replicative niche:the Coxiella-containing vacuole.We describe the actin-associated proteins involved in the internalization of C.burnetii,and we discuss the contribution of diverse degradation pathways of the cell during the formation and stabilization of the Coxiella-containing vacuole.
基金supported by grants from the National Key Research and Development Projects(2019YFE0103800)Scientific Research Project of Sichuan Provincial Health Department(No.18PJ586)Research and Innovation Team Project of Chengdu Medical College(No.CYTD16-04)。
文摘This study was to explore the immunity-promoting activity of porcine placenta as a potential raw material for functional foods.Porcine placenta was subjected to the analysis for its bioactive substances,and their immunity-promoting activity was determined in mice supplemented with porcine placenta extract(PPE)and freeze-dried porcine placenta powder at high(PPH)and low(PPL)dosage.Results showed that porcine placenta contained placental peptides and 15 free amino acids,and the amounts of estrogen and progesterone in products developed from porcine placenta were within the limit of national standard.Mice model experiment revealed that compared with the control,the PPH treatment significantly improved the spleen index(P<0.05)by increasing the phagocytic rate of macrophages from 20%to 60%and the conversion rate of T lymphocytes from 8%to 60%.The q PCR analysis disclosed that the porcine placenta powder enhanced mice immunity via promoting the expression of Th1 cytokines of interleukin-2(IL-2)and IFN-γ,especially the former,by almost 8 times in the spleens of male mice,while inhibited Th2 cytokines of IL-4 and IL-10.This investigation has provided a reference for the development of porcine placenta as a raw material applied in functional foods to improve human immunity.
文摘Alveolar macrophages (AM) are known to play an essential role in lung defense through their ability to remove the foreign matters reaching the lung alveoli. Cigarette smoke (CS) is a critical risk factor for many lung diseases. CS is inhaled into the lung by respiretion and affects AM. It has been previously reported that CS induces inhibition of cytokine production, cell surface receptor expression and antigen presentation in AM. However, the relationship of immune suppression and DNA damage caused by CS in AM is still unclear. Therefore, in this study, we investigated AM immune function and DNA damage in CS-exposed mice. Mice were exposed to CS of 20 cigarettes/day during 10 days using a HambrugⅡsmoking machine. After exposure, AM were obtained by bronchoalveolar lavage. The number of AM was significantly increased in CS-exposed mice compared with non-CS-exposed mice. Phagocytic activity of AM was significantly inhibited by CS exposure. Percentage of CD11b-, CD14-, Toll-like receptor (TLR)2- or TLR4-positive cells was significantly decreased in CS-exposed mice compared with non-CS-exposed mice. Interleukin-1β mRNA expression in lipopolysaccharide-stimulated AM was significantly inhibited by CS exposure. Intracellular reactive oxygen species (ROS) (, H2O2) production of AM was significantly increased, and DNA damage was induced by CS exposure. These results suggest that impaired immune functions by CS exposure may be related to DNA damage via excessive ROS induced by CS. These alterations of AM caused by CS could be associated with infection and development of pulmonary diseases.
文摘The objective of the current work is to investigate the possible beneficial effects of forced feeding of fenugreek to rabbit does on their milk composition, milk yield, anemia screening parameters, immunity and the growth performance of bunnies. Twenty white New Zealand female rabbits were randomly assigned into 5 groups: normal control and 4 treated groups (vehicle (molasses), fenugreek powdered seeds + molasses, sprouted fenugreek + molasses, and fenugreek oil + molasses). All treated groups took the given doses orally for two days before parturition and 13 days after parturition for 2 successive pregnancies. Blood samples were collected from each doe on the 13<sup>th</sup> day of lactation for determination of hematological, biochemical and immunological parameters. Milk samples were taken for evaluation of milk composition. All rabbit does and their bunnies were weighed for calculation of the milk yield. The fenugreek seeds and oil administered groups (G<sup>3</sup> & G<sup>5</sup>) recorded the highest percent values of fat, protein, lactose, total solids and solid not fat contents of the rabbits’ milk in both 1st and 2nd lactation periods relative to other tested groups. At the beginning and mid of lactation periods, the milk yields recorded non-significant differences either between tested groups or between 1<sup>st</sup> and 2<sup>nd</sup> pregnancy in the same group. Whereas, at the end of lactation, germinated seeds (G<sup>4</sup>) and oil (G<sup>5</sup>) treated groups recorded significantly higher rates of milk yield relative to control and fenugreek seeds groups. Bunnies’ body weights suckling from dams of group III (G<sup>3</sup>) recorded the highest weights relative to other tested groups in both 1<sup>st</sup> and 2<sup>nd</sup> pregnancy. During the 1<sup>st</sup> lactation period, all experimental groups showed significant reduction of white blood cells, while, G<sup>3</sup> and G<sup>4</sup> recorded significant elevation during 2<sup>nd</sup> lactation period. Rabbits treated with fenugreek seeds powder (G<sup>3</sup>) showed a significant raise of phagocytic activity and phagocytic index. Fenugreek seeds group (G<sup>3</sup>) and germinated one (G<sup>4</sup>) showed significant red blood corpuscles and packed cell volume raise relative to other groups during both 1<sup>st</sup> and 2<sup>nd</sup> lactation periods.
基金supported by a grant from State Key Laboratory of Proteomics of China,No.SKLP-K201401(to SJL)the National Key Project of Basic Research of China,No.2009CB918301(to SJL)the National Natural Science Foundation of China,Nos.30430310,30140001,30370460(to SJL)
文摘Microglia, as the resident immune cells in the central nervous system, play important roles in regulating neuronal processes, such as neural excitability, synaptic activity, and apoptotic cell clearance. Growth factors can activate multiple signaling pathways in central nervous system microglia and can regulate their immune effects, but whether growth factors can affect the morphological characteristics and ultrastructure of microglia has not been reported. After microinjecting 300 nL of a growth factor cocktail, including 10 μg/mL epidermal growth factor, 10 μg/mL basic fibroblast growth factor, 10 μg/mL hepatocyte growth factor and 10 μg/mL insulin-like growth factor into adult rat cortex, we found that the number of IBA1-positive microglia around the injection area increased significantly, indicating local activation of microglia. All CD68-positive labeling co-localized with IBA1 in microglia. Cell bodies and protrusions of CD68-positive cells were strongly attached to or were engulfing neurons. Characteristic huge phagosomes were observed in activated phagocytes by electron microscopy. The phagosomes generally included non-degraded neuronal protrusions and mitochondria, yet they contained no myelin membrane or remnants, which might indicate selective phagocytosis by the phagocytes. The remnant myelin sheath after phagocytosis still had regenerative ability and formed "myelin-like" structures around phagocytes. These results show that microinjection of a growth factor cocktail into the cerebral cortex of rodents can locally activate microglia and induce selective phagocytosis of neural structures by phagocytes. The study was approved by the Institute of Laboratory Animal Science, Beijing Institute of Basic Medical Sciences(approval No. IACUC-AMMS-2014-501) on June 30, 2014.
文摘Background: Glucose is the main substrate for the generation of NADPH, the cofactor of the oxidative burst enzyme NADPH-oxidase of blood neutrophils. Changes in blood glucose are thus expected to modify the generation of reactive oxygen species (ROS). The new blood ROS generation assay (BRGA) quantifies ROS changes induced by blood glucose concentrations as they are found in diabetes mellitus. Material and Methods: Citrated or EDTA blood of 6 healthy donors were analyzed in the BRGA: 10 μl sample in black polystyrene F-microwells (Brand 781608) were incubated in triplicate with 125 μl Hanks’ balanced salt solution, 40 μl 0 - 200 mM glucose in 0.9% NaCl (final added conc.: 0 - 41 mM;final basal glucose conc.: about4 mM), 10 μl5 mMluminol, and 10 μl zymosan A (final conc.: 1.9 μg/ml) in 0.9% NaCl. The plates were measured within 0 - 250 min (37℃) in a photons-multiplyer microtiter plate luminometer (LUmo) with an integration time of 1 s. Results: Up to about 30 min reaction time the mean ROS generation was 50% inhibited by about1 mMadded glucose (= approx. IC50). At ≥80 min reaction time (possibly necessary for full phosphorylation of glucose to glucose-6-phosphate (G6P), the substrate metabolized by G6P-dehydrogenase to generate NADPH, the cofactor of the NADPH-oxidase) the mean ROS generation approximately doubled at about1 mMadded glucose (= approx. SC200) in citrated blood. Discussion: Elevated glucose concentrations not only increase systemic thrombin generation, they can also diminish cellular fibrinolysis and increase systemic inflammation, resulting in a chronic pro-thrombotic state. The fascinating importance of NADPH-oxidases not only in phagocytes but also in the beta cells of pancreas points towards a new pathogenesis explication of diabetes mellitus type 1: whatever stimulus (e.g. a pancreas-tropic virus) could activate the beta cell’s autodestructive NADPH-oxidase.
基金Supported by the Research project “Implication of phagocytes dependent oxidative stress in inflammatory diseases and leishmaniasis” with project No.CNEPRU F00220130061Algerian Ministry of Higher Education and Scientific Research
文摘Objective: To investigate the leishmanicidal effects of two antioxidants, caffeic acid and quercetin on Leishmania major(L.major) promastigotes in vitro, and their immunomodulatory effects on infected phagocytes derived from susceptible BALB/c mice.Methods: Caffeic acid and quercetin-induced cell death was examined by Pi-Hoechst double staining of L.major promastigotes and MTT assay, in the presence or absence of protease inhibitors in vitro.Caffeic acid or quercetin were administered subcutaneously to BALB/c mice infected with L.major promastigotes through a dorsal air pouch.Nitric oxide and superoxide anion production by phagocytes infiltrating the air pouch and the expression of inducible nitric oxide synthase(i NOS), tumor necrosis factor alpha(TNF-a) and nuclear factor kappa B in the air pouch membrane were therefore evaluated using appropriate methods.Results: Caffeic acid and quercetin displayed a dose-dependent cytotoxic effect against L.major promastigotes, and induced cell death via caspases-independent pathways.In vivo, L.major promastigotes inoculation into air pouch cavity of BALB/c mice leads to a sequential influx of neutrophils(hours), followed by macrophages(days).Results showed that L.major delayed apoptosis of infected neutrophils and macrophages by the cleavage of the nuclear factor kappa B p65^(RelA) subunit, and persisted by inhibiting TNF-a and i NOS expression and reactive oxygen species generation.Caffeic acid or quercetin restored reactive oxygen species production and TNF-a-induced i NOS activity, and abrogate apoptosis delay of infected phagocytes.Conclusions: The leishmanicidal effect of caffeic acid and quercetin on promastigotes and amastigotes, as well as reactivation of infected phagocytes apoptosis, suggested a potential therapeutic role against cutaneous leishmaniasis.
基金National Natural Science Foundation of China,No 81970529The Natural Science Foundation of Jilin Province,No.20200201387JC.
文摘The mononuclear phagocyte system(MPS)consists of monocytes,dendritic cells and macrophages,which play vital roles in innate immune defense against cancer.Hepatocellular carcinoma(HCC)is a complex disease that is affected or initiated by many factors,including chronic hepatitis B virus infection,hepatitis C virus infection,metabolic disorders or alcohol consumption.Liver function,tumor stage and the performance status of patients affect HCC clinical outcomes.Studies have shown that targeted treatment of tumor microenvironment disorders may improve the efficacy of HCC treatments.Cytokines derived from the innate immune response can regulate T-cell differentiation,thereby shaping adaptive immunity,which is associated with the prognosis of HCC.Therefore,it is important to elucidate the function of the MPS in the progression of HCC.In this review,we outline the impact of HCC on the MPS.We illustrate how HCC reshapes MPS cell phenotype remodeling and the production of associated cytokines and characterize the function and impairment of the MPS in HCC.
基金Supported by grants from CONICET(Argentina,EM,PIP-CONICET 112-201101-00247,http://www.conicet.gov.ar)ANPCyT(Argentina,EM,PICT 2012-174,PICT 2017-499+1 种基金http://www.agencia.mincyt.gob.ar)NIH-CONICET(Argentina and USA,EM and Stephen Noctor,F65096).
文摘Until recently,microglia were mainly known as the resident phagocytes of the brain,i.e.the‘immunological warriors’of the brain.However,extensive knowledge is being accumulated about the functions of microglia beyond immunity.Nowadays,it is well accepted that microglial cells are highly dynamic and responsive,and that they intervene in a dual manner in many developmental processes that shape the central nervous system,including neurogenesis,gliogenesis,spatial patterning,synaptic formation and elimination,and neural circuit establishment and maturation.The differentiation and the pool of precursor cells were also shown to be under microglia regulation via bidirectional communication.In this concise review,I discuss our recent work in microglia-Pax6+cell interactions in one of the circumventricular organs,the pineal gland.An analogy with the rest of the central nervous system is also presented.In addition,I briefly examine mechanisms of interaction between microglia and non-microglial cells in both health and disease.New avenues are also introduced,which may lead us to better comprehend the impact of microglia in physiological and pathological conditions.
文摘The aim of this study is to evaluate the effect of moderate physical exercise and treatment time on the organism’s response to NSC631570. The sensitivity of circulating phagocytes to the drug at different times of day was estimated in in vitro experiments. NSC631570 was administered intravenously to healthy volunteers (eleven men, 23 ± 2 years) in a single therapeutic dose in an inpatient and an outpatient setting. Blood samples were obtained before the drug administration, 30 min after the drug injection and every fourth hour throughout the 24 hour period. Biochemical parameters were determined using the hematological analyzer. Flow cytometry was used to evaluate phagocyte metabolism. Treatment of circulating phagocytes with NSC631570 in vitro resulted in an increase in ROS production along with a decrease in their phagocytic activity, most expressed in the morning time. Drug injection to sedentary persons resulted in pro-inflammatory metabolic polarization of circulating phagocytes. Introduction of NSC631570 to active persons was accompanied by a significant increase in phagocyte endocytosis along with a decrease in the daily mean of ROS generation. Significant oscillation (but in the normal ranges) of urea, creatinine, alanine aminotransferase and aspartate aminotransferase after NSC631570 introduction in the outpatient setting was shown during the day. Physical activity interferes with immunomodulatory action of NSC631570 and abrogates pro-inflammatory shift of circulating phagocytes. Biochemical parameters of blood from patients treated with NSC631570 in the outpatient setting must be interpreted cautiously considering the effect of physical activity on some metabolic biomarkers.
文摘The capacities of phagocytes of subpopulation P1 (F) and morula cells (MC) of holothurian Eupentacta fraudatrix to modulate apoptosis of each other as well as cytokine-dependent mechanisms and hormonal regulation of these cells’s interaction were studied. The 18-h treatment of F with supernatants, obtained after centrifugation of MC preincubated for 3 h with phosphate buffered saline (PSB) at the temperature of 22℃?(SMC3) resulted in a significant growth of apoptosis level. A 30-min incubation of F with supernatants of MC, preincubated for 24 h (SMC24), on the contrary, reduced the apoptosis level and increased the level of interleukine-1α (IL-1α)-like substances, and 24-h incubation did not influence apoptosis and reduced level of IL-1α-like substances. Thus, proapoptotic effects of MC’s supernatants in F inversely depended on time of their preincubation with PSB and directly on time of incubation with F. Additionally, this effect was opposite to variations in the level of IL-1α-like substances. The level of apoptosis declined after 30 min of incubation but elevated after 24 h at the inverse treatment of MC with supernatant, obtained after preincubation of F during 24 h (SF24). The level of IL-1α-like substances dropped after 30 min and insignificantly decreased after 24 h. Hence, SF24 proapoptotic effect directly depended on time of incubation with MC and did not correspond to variations in the level of IL-1α-like substances. 100 μM dexamethasone stimulated apoptosis in F and MC in an inverse time-dependent manner during 24-h preincubation, and supernatants of cell suspensions obtained after such preincubations, stimulated apoptosis and reduced the IL-1α-like substances level in target cells at both types of interaction. IL-1α-like substances are?supposed to be mediators for MC’s effects in F, but not for F’s action on MC. In holothurians, steroid hormones apparently may participate in the regulation of the immune response and cell cooperation.
