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

First Author  Machado ID Year  2014
Journal  Am J Physiol Endocrinol Metab Volume  307
Issue  9 Pages  E754-63
PubMed ID  25184992 Mgi Jnum  J:215552
Mgi Id  MGI:5605616 Doi  10.1152/ajpendo.00227.2014
Citation  Machado ID, et al. (2014) Alterations in the profile of blood neutrophil membrane receptors caused by in vivo adrenocorticotrophic hormone actions. Am J Physiol Endocrinol Metab 307(9):E754-63
abstractText  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 mug 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-1alpha)-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.
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