Annexin A1 Is a Physiological Modulator of Neutrophil Maturation and Recirculation Acting on the CXCR4/CXCL12 Pathway

Autor(es)

Machado, Isabel Daufenback ; Spatti, Marina ; Hastreiter, Araceli ; Santin, Jose Roberto ; Fock, Ricardo Ambrosio ; Gil, Cristiane Damas ; Oliani, Sonia Maria ; Perretti, Mauro ; Poliselli Farsky, Sandra Helena

• Tipo de documento: Artigo Científico
• Fonte: Journal of Cellular Physiology; v. 231, n. 11, p. 2418-2427, NOV 2016.
• Citações Web of Science: 8

Resumo

Neutrophil production and traffic in the body compartments is finely controlled, and the strong evidences support the role of CXCL12/CXCR4 pathway on neutrophil trafficking to and from the bone marrow (BM). We recently showed that the glucocorticoid-regulated protein, Annexin A1 (AnxA1) modulates neutrophil homeostasis and here we address the effects of AnxA1 on steady-state neutrophil maturation and trafficking. For this purpose, AnxA1(-/-) and Balb/C wild-type mice (WT) were donors of BM granulocytes and mesenchymal stem cells and blood neutrophils. In vivo treatments with the pharmacological AnxA1 mimetic peptide (Ac2-26) or the formyl peptide receptor (FPR) antagonist (Boc-2) were used to elucidate the pathway of AnxA1 action, and with the cytosolic glucocorticoid antagonist receptor RU 38486. Accelerated maturation of BM granulocytes was detected in AnxA1(-/-) and Boc2-treated WT mice, and was reversed by treatment with Ac2-26 in AnxA1(-/-) mice. AnxA1 and FPR2 were constitutively expressed in bone marrow granulocytes, and their expressions were reduced by treatment with RU38486. Higher numbers of CXCR4(+) neutrophils were detected in the circulation of AnxA1(-/-) or Boc2-treated WT mice, and values were rescued in Ac2-26-treated AnxA1(-/-) mice. Although circulating neutrophils of AnxA1(-/-) animals were CXCR4(+), they presented reduced CXCL12-induced chemotaxis. Moreover, levels of CXCL12 were reduced in the bone marrow perfusate and in the mesenchymal stem cell supernatant from AnxA1(-/-) mice, and in vivo and in vitro CXCL12 expression was re-established after Ac2-26 treatment. Collectively, these data highlight AnxA1 as a novel determinant of neutrophil maturation and the mechanisms behind blood neutrophil homing to BM via the CXCL12/CXCR4 pathway. (C) 2016 Wiley Periodicals, Inc. (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: 14/07328-4 - Identificação de vias endógenas para o controle da inflamação
• Beneficiário: Sandra Helena Poliselli Farsky
• Modalidade de apoio: Auxílio à Pesquisa - Temático