VCAM-1-mediated Rac signaling controls endothelial cell-cell contacts and leukocyte transmigration.
Am J Physiol Cell Physiol
; 285(2): C343-52, 2003 Aug.
Article
em En
| MEDLINE
| ID: mdl-12700137
ABSTRACT
Leukocyte adhesion is mediated totally and transendothelial migration partially by heterotypic interactions between the beta1- and beta2-integrins on the leukocytes and their ligands, Ig-like cell adhesion molecules (Ig-CAM), VCAM-1, and ICAM-1, on the endothelium. Both integrins and Ig-CAMs are known to have signaling capacities. In this study we analyzed the role of VCAM-1-mediated signaling in the control of endothelial cell-cell adhesion and leukocyte transendothelial migration. Antibody-mediated cross-linking of VCAM-1 on IL-1beta-activated primary human umbilical vein endothelial cells (pHUVEC) induced actin stress fiber formation, contractility, and intercellular gaps. The effects induced by VCAM-1 cross-linking were inhibited by C3 toxin, indicating that the small GTPase p21Rho is involved. In addition, the effects of VCAM-1 were accompanied by activation of Rac, which we recently showed induce intercellular gaps in pHUVEC in a Rho-dependent fashion. With the use of a cell-permeable peptide inhibitor, it was shown that Rac signaling is required for VCAM-1-mediated loss of cell-cell adhesion. Furthermore, VCAM-1-mediated signaling toward cell-cell junctions was accompanied by, and dependent on, Rac-mediated production of reactive oxygen species and activation of p38 MAPK. In addition, it was found that inhibition of Rac-mediated signaling blocks transendothelial migration of monocytic U937 cells. Together, these data indicate that VCAM-1-induced, Rac-dependent signaling plays a key role in the modulation of vascular-endothelial cadherin-mediated endothelial cell-cell adhesion and leukocyte extravasation.
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Base de dados:
MEDLINE
Assunto principal:
Endotélio Vascular
/
Adesão Celular
/
Comunicação Celular
/
Quimiotaxia de Leucócito
/
Molécula 1 de Adesão de Célula Vascular
/
Proteínas rac de Ligação ao GTP
/
Leucócitos
Limite:
Humans
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article