Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Exp Med. Feb 20, 2017; 7(1): 11-24
Published online Feb 20, 2017. doi: 10.5493/wjem.v7.i1.11
Odd couple: The unexpected partnership of glucocorticoid hormones and cysteinyl-leukotrienes in the extrinsic regulation of murine bone-marrow eosinopoiesis
Pedro Xavier-Elsas, Daniela Masid-de-Brito, Bruno Marques Vieira, Maria Ignez C Gaspar-Elsas
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
Bruno Marques Vieira, Maria Ignez C Gaspar-Elsas, Department Pediatrics, Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira, FIOCRUZ, Rio de Janeiro 22250-020, Brazil
Author contributions: All authors contributed to this manuscript.
Conflict-of-interest statement: The authors declare no conflicting interests exist related to this article.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Pedro Xavier-Elsas, MD, PhD, Associate Professor, Department Immunology, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Bloco I, Room I-2-066, Rio de Janeiro 21941-590, Brazil.
Telephone: +55-21-996360108
Received: September 13, 2016
Peer-review started: September 14, 2016
First decision: October 21, 2016
Revised: November 1, 2016
Accepted: November 27, 2016
Article in press: November 29, 2016
Published online: February 20, 2017

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 eosinopoiesis in vivo and in vitro. CysLT 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 CysLT 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 CysLT-mediated upregulation of bone-marrow eosinopoiesis in vivo, but also attenuate subsequent ex vivo responses 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.

Keywords: Bone marrow, Leukotriene, Eosinophil, Stress, Glucocorticoid

Core tip: The bone-marrow is exquisitely sensitive to regulation by systemic events, which selectively increase production of different blood cell types to meet transient increases in demand following injury. An association between stress and allergy has long been known, but its mechanisms remain incompletely understood. The exploration of underlying mechanisms in a variety of murine models yielded evidence of separate but interrelated roles for adrenal glucocorticoid hormones and cysteinyl-leukotrienes in coupling systemic events to bone-marrow responses in vivo. We here discuss how these unlikely partners work together to promote eosinophilia but through subtle mechanisms also limit its magnitude.