Alterations in the profile of blood neutrophil membrane receptors caused by in vivo adrenocorticotrophic hormone actions

Alterations in the profile of blood neutrophil membrane receptors caused by in vivo adrenocorticotrophic hormone actions

Author Machado, Isabel Daufenback Google Scholar
Santin, Jose Roberto Google Scholar
Drewes, Carine Cristiane Google Scholar
Gil, Cristiane Damas Autor UNIFESP Google Scholar
Oliani, Sonia Maria Google Scholar
Perretti, Mauro Google Scholar
Poliselli Farsky, Sandra Helena Google Scholar
Institution Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
São Paulo State Univ
Queen Mary Univ London
Abstract Elevated levels of adrenocorticotrophic hormone (ACTH) mobilize granulocytes from bone marrow into the blood, although these neutrophils are refractory to a full migratory response into inflamed tissues. Here, we investigated the dependence of glucocorticoid receptor activation and glucocorticoid-regulated protein annexin A1 (ANXA1) on ACTH-induced neutrophilia and the phenotype of blood neutrophil after ACTH injection, focusing on adhesion molecule expressions and locomotion properties. ACTH injection (5 mu g ip, 4 h) induced neutrophilia in wild-type (WT) mice and did not alter the elevated numbers of neutrophils in RU-38486 (RU)-pretreated or ANXA1(-/-)mice injected with ACTH. Neutrophils from WT ACTH-treated mice presented higher expression of Ly6G(+) ANXA1(high), CD18(high), CD62L(high), CD49(high), CXCR4(high), and formyl-peptide receptor 1 (FPR1(low)) than those observed in RU-pretreated or ANXA1(-/-)mice. the membrane phenotype of neutrophils collected from WT ACTH-treated mice was paralleled by elevated fractions of rolling and adherent leukocytes to the cremaster postcapillary venules together with impaired neutrophil migration into inflamed air pouches in vivo and in vitro reduced formyl-methionyl-leucyl-phenylalanine (fMLP) or stromal-derived factor-1 (SDF-1 alpha)-induced chemotaxis. in an 18-h senescence protocol, neutrophils from WT ACTH-treated mice had a higher proportion of ANXAV(low)/CXCR4(low), and they were less phagocytosed by peritoneal macrophages. We conclude that alterations on HPA axis affect the pattern of membrane receptors in circulating neutrophils, which may lead to different neutrophil phenotypes in the blood. Moreover, ACTH actions render circulating neutrophils to a phenotype with early reactivity, such as in vivo leukocyte-endothelial interactions, but with impaired locomotion and clearance.
Keywords hypothalamic-pituitary-adrenal axis
chemokine (C-X-C motif) receptor 4
adhesion molecules
intravital microscopy
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number FAPESP: 2010/16828-0
: 2010/08402-2
: 2010/17175-0
: 2010/19802-1
Date 2014-11-01
Published in American Journal of Physiology-endocrinology and Metabolism. Bethesda: Amer Physiological Soc, v. 307, n. 9, p. E754-E763, 2014.
ISSN 0193-1849 (Sherpa/Romeo, impact factor)
Publisher Amer Physiological Soc
Extent E754-E763
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000344989400003

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