Odd couple: The unexpected partnership of glucocorticoid hormones and cysteinyl-leukotrienes in the extrinsic regulation of murine bone-marrow eosinopoiesis

作     者：Pedro Xavier-Elsas Daniela Masid-de-Brito Bruno Marques Vieira Maria Ignez C Gaspar-Elsas 

作者机构：Department Immu-nologyInstituto de Microbiologia Paulo de GóesUniversidade Federal do Rio de Janeiro Department PediatricsInstituto Nacional de Saúde da Mulherda Crian?a e do Adolescente Fernandes FigueiraFIOCRUZ 

出 版 物：《World Journal of Experimental Medicine》 (世界实验医学杂志)

年 卷 期：2017年第7卷第1期

页      面：11-24页

学科分类：10[医学] 

主　　题：Bone marrow Leukotriene Eosinophil Stress Glucocorticoid 

摘      要：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.