title: Alterations in the profile of blood neutrophil membrane receptors caused by in vivo adrenocorticotrophic hormone actions.
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 μg 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-1α)-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.
authors.affiliation: Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil;
authors.forename: Isabel Daufenback
authors.initials: ID
authors.lastname: Machado
authors.affiliation: Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil;
authors.forename: José Roberto
authors.initials: JR
authors.lastname: Santin
authors.affiliation: Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil;
authors.forename: Carine Cristiane
authors.initials: CC
authors.lastname: Drewes
authors.affiliation: Department of Morphology and Genetics, Federal University of São Paulo, Sao Paulo, Brazil;
authors.forename: Cristiane Damas
authors.initials: CD
authors.lastname: Gil
authors.affiliation: Department of Biology, Instituto de Biociências, Letras e Ciências Exatas, São Paulo State University, São José do Rio Preto, Brazil; and.
authors.forename: Sonia Maria
authors.initials: SM
authors.lastname: Oliani
authors.affiliation: The William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London, London, United Kingdom.
authors.forename: Mauro
authors.initials: M
authors.lastname: Perretti
authors.affiliation: Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil; sfarsky@usp.br.
authors.forename: Sandra Helena Poliselli
authors.initials: SH
authors.lastname: Farsky
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D000818:Animals; D017305:Annexin A1 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003345:Corticosterone / Q000097:blood / Q000378:metabolism; D006727:Hormone Antagonists / Q000494:pharmacology; D019891:Leukopoiesis / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D010587:Phagocytosis / Q000187:drug effects; D018043:Receptors, Corticotropin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D013312:Stress, Physiological / Q000187:drug effects; D013315:Stress, Psychological / Q000097:blood / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013499:Surface Properties / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D017305:Annexin A1; D006727:Hormone Antagonists; D018043:Receptors, Corticotropin; C573274:annexin A1, mouse; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone
keywords: adhesion molecules; chemokine (C-X-C motif) receptor 4; chemotaxis; hypothalamic-pituitary-adrenal axis; intravital microscopy