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

Author(s)

Machado, Isabel Daufenback ^[1] ; Santin, Jose Roberto ^[1] ; Drewes, Carine Cristiane ^[1] ; Gil, Cristiane Damas ^[2] ; Oliani, Sonia Maria ^[3] ; Perretti, Mauro ^[4] ; Poliselli Farsky, Sandra Helena ^[1]

Affiliation

^[1] Univ Sao Paulo, Fac Pharmaceut Sci, Dept Clin & Toxicol Analyses, BR-05508900 Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Dept Morphol & Genet, Sao Paulo - Brazil

^[3] Sao Paulo State Univ, Inst Biociencias Letras & Ciencias Exatas, Dept Biol, Sao Jose Do Rio Preto - Brazil

^[4] Queen Mary Univ London, Barts & London Sch Med, William Harvey Res Inst, London - England

• Document type: Journal article
• Source: AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM; v. 307, n. 9, p. E754-E763, NOV 1 2014.
• Web of Science Citations: 3

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. (AU)

• FAPESP's process: 10/19802-1 - Effects of lipid-core nanocapsules with acetyleugenol in melanomas: in vivo and in vitro studies
• Grantee: Carine Cristiane Drewes
• Support type: Scholarships in Brazil - Doctorate
• FAPESP's process: 10/08402-2 - Role of endogenous glucocorticoids and annexin A1 on neutrophil migration: involvement of SDF1 alpha/CXCR-4 and IL-17/IL-23
• Grantee: Isabel Daufenback Machado
• Support type: Scholarships in Brazil - Doctorate
• FAPESP's process: 10/17175-0 - Effect of PPAR agonist LYSO-07 on installation and healing of gastric ulcers in mice
• Grantee: José Roberto Santin
• Support type: Scholarships in Brazil - Doctorate
• FAPESP's process: 10/16828-0 - Molecular mechanisms of endogenous glucocorticoids on neutrophil traffic: actions on SDF-1alfa/CXCR-4 and IL-17/IL-23/G-CSF axis
• Grantee: Sandra Helena Poliselli Farsky
• Support type: Regular Research Grants