| Autor: |
van Wetering, Sandra, van den Berk, Nadia, van Buul, Jaap D., Mul, Frederik P.J., Lommerse, Ingrid, Mous, Rogier, ten Klooster, Jean-Paul, Zwaginga, Jaap-Jan, Hordijk, Peter L. |
| Předmět: |
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| Zdroj: |
American Journal of Physiology: Cell Physiology; Aug2003, Vol. 285 Issue 2, pC343, 10p, 10 Color Photographs, 1 Diagram, 8 Graphs |
| Abstrakt: |
Leukocyte adhesion is mediated totally and transendothelial migration partially by heterotypic interactions between the β[sub 1]- and β[sub 2]-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-1β-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 cellpermeable 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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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