Mecanismos celulares e moleculares de ação dos glicocorticóides endógenos sobre a mobilização de neutrófilos / Cellular and molecular mechanisms of action of endogenous glucocorticoids on the neutrophil mobilization

AUTOR(ES)

Danielle Maia de Holanda Cavalcanti

DATA DE PUBLICAÇÃO

2010

RESUMO

We have shown that endogenous glucocorticoids (GE) modulate the rolling and adhesion of neutrophils in vivo, mediating the expression of adhesion molecules on leukocytes and the endothelium. Additionally, the GE control neutrophil maturation in bone marrow and mobilization to peripheral blood. This work aimed to investigate the molecular and cellular mechanisms involved in the modulation exerted by GE in this process. Using male Wistar rats, submitted to bilateral adrenalectomy, treatment with RU 38 486 or controls (sham operated, vehicle or non manipulated), it was shown that: 1) GE control, negatively, L-selectin expression on circulating neutrophils and ICAM-1, VCAM-1, PECAM-1, VAP-1 on endothelial cell and, positively, L-selectin expression on bone marrow granulocytes via their cytosolic receptor (GCR); 2) the mechanism involved in the control of GE on the L-selectin expression is independent of its action on gene expression or NFkB activity, but dependent on the expression of anexina-A1, as observed in mice knockouts for this protein; 3) the control of endothelial adhesion molecules is dependent on gene expression, via NFkB translocation; 4) the neutrophilia detected in adrenalectomized animals (ADR) is mediated by GCR, and dependent on anexina-A1; 5) the neutrophilia seems to be dependent on the action of annexin A-1 on SDF-1α secretion in bone marrow and expression of CXCR-4 in peripheral blood and bone marrow; 6) high circulating concentrations of GE induced by administration of ACTH confirmed the control of GE, via the annexin-1, on the traffic of neutrophils from the bone marrow to the blood, but suggest a differential control of GE and annexin A-1 on the L-selectin expression in the bone marrow and circulating blood. These data indicate unpublished mechanisms of control of GE on the traffic of neutrophils, which differ in each microenvironment and cell type involved in this complex phenomenon.

ASSUNTO(S)

glicocorticóides glucocorticoids annexin a-1 neutrophils moléculas de adesão anexina a-1 adhesion molecules neutrófilos

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