Granulopoiesis in murine bone-marrow is regulated by both intrinsic and extrinsic factors(including hormones, drugs, inflammatory mediators and cytokines). Eosinophils, a minor subpopulation of circulating leukocytes,...Granulopoiesis in murine bone-marrow is regulated by both intrinsic and extrinsic factors(including hormones, drugs, inflammatory mediators and cytokines). Eosinophils, a minor subpopulation of circulating leukocytes, which remains better understood in its contributions to tissue injury in allergic disease than in its presumably beneficial actions in host defense, provide a striking example of joint regulation of granulopoiesis within murine bone-marrow by all of these classes of extrinsic factors. We first described the upregulation of eosinopoiesis in bone-marrow of allergen-sensitized mice following airway allergen challenge. Over the last decade, we were able to show a critical role for endogenous glucocorticoid hormones and cytokines in mediating this phenomenon through modification of cytokine effects, thereby supporting a positive association between stress hormones and allergic reactions. We have further shown that cysteinylleukotrienes(Cys LT), a major proinflammatory class of lipid mediators, generated through the 5-lipoxygenase pathway, upregulate bone-marrow eosinopoiesis in vivo and in vitro. Cys LT mediate the positive effects of drugs(indomethacin and aspirin) and of proallergic cytokines(eotaxin/CCL11 and interleukin-13) on in vitro eosinopoiesis. While these actions of endogenous GC and Cys LT might seem unrelated and even antagonistic, we demonstrated a critical partnership of these mediators in vivo, shedding light on mechanisms linking stress to allergy: GC are required for Cys LT-mediated upregulation of bone-marrow eosinopoiesis in vivo, but also attenuate subsequent ex vivo responses to Cys LT. GC and Cys LT therefore work together to induce eosinophilia, but through subtle regulatory mechanisms also limit the magnitude of subsequent bone-marrow responses to allergen.展开更多
AIM: To determine whether online diffusion of the "Ten Warning Signs of Primary Immunodeficiency Diseases(PID)'' adheres to accepted scientific standards.METHODS: We analyzed how reproducible is online di...AIM: To determine whether online diffusion of the "Ten Warning Signs of Primary Immunodeficiency Diseases(PID)'' adheres to accepted scientific standards.METHODS: We analyzed how reproducible is online diffusion of a unique instrument, the "Ten Warning Signs of PID", created by the Jeffrey Modell Foundation(JMF),by Google-assisted searches among highly visited sites from professional, academic and scientific organizations;governmental agencies; and patient support/advocacy organizations. We examined the diffusion, consistency of use and adequate referencing of this instrument.Where applicable, variant versions of the instrument were examined for changes in factual content that would have practical impact on physicians or on patients and their families.RESULTS: Among the first 100 sites identified by Google search, 85 faithfully reproduced the JMF model, and correctly referenced to its source. By contrast, the other15 also referenced the JMF source but presented one or more changes in content relative to their purported model and therefore represent uncontrolled variants, of unknown origin. Discrepancies identified in the latter included changes in factual content of the original JMF list(C), as well as removal(R) and introduction(I) of novel signs(Table 2), all made without reference to any scientific publications that might account for the drastic changes in factual content. Factual changes include changes inthe number of infectious episodes considered necessary to raise suspicion of PID, as well as the inclusion of various medical conditions not mentioned in the original.Together, these changes will affect the way physicians use the instrument to consult or to inform patients,and the way patients and families think about the need for specialist consultation in view of a possible PID diagnosis.CONCLUSION: The retrieved adaptations and variants,which significantly depart from the original instrument,raise concerns about standards for scientific information provided online to physicians, patients and families.展开更多
Bone marrow, the vital organ which maintains lifelong hemopoiesis, currently receives considerable attention, as a source of multiple cell types which may play important roles in repair at distant sites. This emerging...Bone marrow, the vital organ which maintains lifelong hemopoiesis, currently receives considerable attention, as a source of multiple cell types which may play important roles in repair at distant sites. This emerging function, distinct from, but closely related to, bone marrow roles in innate immunity and inflammation, has been characterized through a number of strategies. However, the use of surgical models in this endeavour has hitherto been limited. Surgical strategies allow the experimenter to predetermine the site, timing, severity and invasiveness of injury; to add or remove aggravating factors(such as infection and defects in immunity) in controlled ways; and to manipulate the context of repair, including reconstitution with selected immune cell subpopulations. This endows surgical models overall with great potential for exploring bone marrow responses to injury, inflammation and infection, and its roles in repair and regeneration. We review three different murine surgical models, which variously combine trauma with infection, antigenic stimulation, or immune reconstitution, thereby illuminating different aspects of the bone marrow response to systemic injury in sepsis, trauma and allergy. They are:(1) cecal ligation and puncture, a versatile model of polymicrobial sepsis;(2) egg white implant, an intriguing model of eosinophilia induced by a combination of trauma and sensitization to insoluble allergen; and(3) ectopic lung tissue transplantation, which allows us to dissect afferent and efferent mechanisms leading to accumulation of hemopoietic cells in the lungs. These models highlight the gain in analytical power provided by the association of surgical and immunological strategies.展开更多
文摘Granulopoiesis in murine bone-marrow is regulated by both intrinsic and extrinsic factors(including hormones, drugs, inflammatory mediators and cytokines). Eosinophils, a minor subpopulation of circulating leukocytes, which remains better understood in its contributions to tissue injury in allergic disease than in its presumably beneficial actions in host defense, provide a striking example of joint regulation of granulopoiesis within murine bone-marrow by all of these classes of extrinsic factors. We first described the upregulation of eosinopoiesis in bone-marrow of allergen-sensitized mice following airway allergen challenge. Over the last decade, we were able to show a critical role for endogenous glucocorticoid hormones and cytokines in mediating this phenomenon through modification of cytokine effects, thereby supporting a positive association between stress hormones and allergic reactions. We have further shown that cysteinylleukotrienes(Cys LT), a major proinflammatory class of lipid mediators, generated through the 5-lipoxygenase pathway, upregulate bone-marrow eosinopoiesis in vivo and in vitro. Cys LT mediate the positive effects of drugs(indomethacin and aspirin) and of proallergic cytokines(eotaxin/CCL11 and interleukin-13) on in vitro eosinopoiesis. While these actions of endogenous GC and Cys LT might seem unrelated and even antagonistic, we demonstrated a critical partnership of these mediators in vivo, shedding light on mechanisms linking stress to allergy: GC are required for Cys LT-mediated upregulation of bone-marrow eosinopoiesis in vivo, but also attenuate subsequent ex vivo responses to Cys LT. GC and Cys LT therefore work together to induce eosinophilia, but through subtle regulatory mechanisms also limit the magnitude of subsequent bone-marrow responses to allergen.
文摘AIM: To determine whether online diffusion of the "Ten Warning Signs of Primary Immunodeficiency Diseases(PID)'' adheres to accepted scientific standards.METHODS: We analyzed how reproducible is online diffusion of a unique instrument, the "Ten Warning Signs of PID", created by the Jeffrey Modell Foundation(JMF),by Google-assisted searches among highly visited sites from professional, academic and scientific organizations;governmental agencies; and patient support/advocacy organizations. We examined the diffusion, consistency of use and adequate referencing of this instrument.Where applicable, variant versions of the instrument were examined for changes in factual content that would have practical impact on physicians or on patients and their families.RESULTS: Among the first 100 sites identified by Google search, 85 faithfully reproduced the JMF model, and correctly referenced to its source. By contrast, the other15 also referenced the JMF source but presented one or more changes in content relative to their purported model and therefore represent uncontrolled variants, of unknown origin. Discrepancies identified in the latter included changes in factual content of the original JMF list(C), as well as removal(R) and introduction(I) of novel signs(Table 2), all made without reference to any scientific publications that might account for the drastic changes in factual content. Factual changes include changes inthe number of infectious episodes considered necessary to raise suspicion of PID, as well as the inclusion of various medical conditions not mentioned in the original.Together, these changes will affect the way physicians use the instrument to consult or to inform patients,and the way patients and families think about the need for specialist consultation in view of a possible PID diagnosis.CONCLUSION: The retrieved adaptations and variants,which significantly depart from the original instrument,raise concerns about standards for scientific information provided online to physicians, patients and families.
文摘Bone marrow, the vital organ which maintains lifelong hemopoiesis, currently receives considerable attention, as a source of multiple cell types which may play important roles in repair at distant sites. This emerging function, distinct from, but closely related to, bone marrow roles in innate immunity and inflammation, has been characterized through a number of strategies. However, the use of surgical models in this endeavour has hitherto been limited. Surgical strategies allow the experimenter to predetermine the site, timing, severity and invasiveness of injury; to add or remove aggravating factors(such as infection and defects in immunity) in controlled ways; and to manipulate the context of repair, including reconstitution with selected immune cell subpopulations. This endows surgical models overall with great potential for exploring bone marrow responses to injury, inflammation and infection, and its roles in repair and regeneration. We review three different murine surgical models, which variously combine trauma with infection, antigenic stimulation, or immune reconstitution, thereby illuminating different aspects of the bone marrow response to systemic injury in sepsis, trauma and allergy. They are:(1) cecal ligation and puncture, a versatile model of polymicrobial sepsis;(2) egg white implant, an intriguing model of eosinophilia induced by a combination of trauma and sensitization to insoluble allergen; and(3) ectopic lung tissue transplantation, which allows us to dissect afferent and efferent mechanisms leading to accumulation of hemopoietic cells in the lungs. These models highlight the gain in analytical power provided by the association of surgical and immunological strategies.
