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

Autor(es)

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM; v. 307, n. 9, p. E754-E763, NOV 1 2014.
• Citações Web of Science: 3

Resumo

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)

• Processo FAPESP: 10/16828-0 - Mecanismos moleculares de ação dos glicocorticóides endógenos sobre o tráfego de neutrófilos: caracterização da ação sobre os eixos SDF-1alfa/CXCR-4 e IL-17/IL-23/G-CSF
• Beneficiário: Sandra Helena Poliselli Farsky
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 10/19802-1 - Efeitos das nanocápsulas de núcleo lipídico contendo acetileugenol em melanomas: estudos in vivo e in vitro
• Beneficiário: Carine Cristiane Drewes
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 10/17175-0 - Efeito do agonista PPAR Lyso-07 sobre a instalação e cicatrização de úlceras gástricas induzidas em camundongos
• Beneficiário: José Roberto Santin
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 10/08402-2 - Efeito dos gliccoorticóides endógenos e da anexina A1 na migração de neutrófilos: envolvimento do eixo SDF-1alfa/CXCR-4 e IL-17/IL-23
• Beneficiário: Isabel Daufenback Machado
• Modalidade de apoio: Bolsas no Brasil - Doutorado