title: Odd couple: The unexpected partnership of glucocorticoid hormones and cysteinyl-leukotrienes in the extrinsic regulation of murine bone-marrow eosinopoiesis.
abstract: 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 cysteinyl-leukotrienes (CysLT), a major proinflammatory class of lipid mediators, generated through the 5-lipoxygenase pathway, upregulate bone-marrow eosinopoiesisin vivoandin vitro. CysLT mediate the positive effects of drugs (indomethacin and aspirin) and of proallergic cytokines (eotaxin/CCL11 and interleukin-13) onin vitroeosinopoiesis. While these actions of endogenous GC and CysLT might seem unrelated and even antagonistic, we demonstrated a critical partnership of these mediatorsin vivo, shedding light on mechanisms linking stress to allergy: GC are required for CysLT-mediated upregulation of bone-marrow eosinopoiesisin vivo, but also attenuate subsequentex vivoresponses to CysLT. GC and CysLT therefore work together to induce eosinophilia, but through subtle regulatory mechanisms also limit the magnitude of subsequent bone-marrow responses to allergen.
authors.affiliation: Pedro Xavier-Elsas, Daniela Masid-de-Brito, Department Immunology, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-590, Brazil.
authors.forename: Pedro
authors.initials: P
authors.lastname: Xavier-Elsas
authors.affiliation: Pedro Xavier-Elsas, Daniela Masid-de-Brito, Department Immunology, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-590, Brazil.
authors.forename: Daniela
authors.initials: D
authors.lastname: Masid-de-Brito
authors.affiliation: Pedro Xavier-Elsas, Daniela Masid-de-Brito, Department Immunology, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-590, Brazil.
authors.forename: Bruno Marques
authors.initials: BM
authors.lastname: Vieira
authors.affiliation: Pedro Xavier-Elsas, Daniela Masid-de-Brito, Department Immunology, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-590, Brazil.
authors.forename: Maria Ignez C
authors.initials: MI
authors.lastname: Gaspar-Elsas
keywords: Bone marrow; Eosinophil; Glucocorticoid; Leukotriene; Stress