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Blood, Vol. 94 No. 4 (August 15), 1999: pp. 1319-1329

Ligation of CD31 (PECAM-1) on Endothelial Cells Increases Adhesive Function of &b.alpha;vbeta 3 Integrin and Enhances beta 1 Integrin-Mediated Adhesion of Eosinophils to Endothelial Cells

Ryuichi Chiba, Noriaki Nakagawa, Kazuhiro Kurasawa, Yoshiya Tanaka, Yasushi Saito, and Itsuo Iwamoto

From the Department of Medicine II, Chiba University School of Medicine, Chiba, Japan; and the Department of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.

We determined the role of the heterophilic interaction of alpha vbeta 3 integrin on endothelial cells with CD31 on leukocytes in mediating leukocyte-endothelial cell interactions. Preincubation of interleukin-4 (IL-4)-stimulated human umbilical vein endothelial cells (HUVECs) with anti-CD31 monoclonal antibodies (MoAbs) enhanced eosinophil adhesion to the IL-4-stimulated HUVECs, and the endothelial CD31-induced enhancement of eosinophil adhesion to IL-4-stimulated HUVECs was prevented by anti-vascular cell adhesion molecule-1 (VCAM-1) MoAb and anti-very late activation antigen-4 (VLA-4) MoAb, but not by anti-intercellular adhesion molecule-1 (ICAM-1) MoAb, anti-lymphocyte function-associated antigen-1 (LFA-1) MoAb, anti-P-selectin MoAb, or anti-E-selectin MoAb. CD31 stimulation of HUVECs increased the adhesive function of alpha vbeta 3 integrin to its ligand RGD peptide, the binding of which reached a maximum at 10 minutes after the stimulation, and the CD31-induced alpha vbeta 3 integrin activation on HUVECs was inhibited by inhibitors of protein kinase C and phosphatidylinositol 3 kinase (PI3-kinase). Furthermore, anti-alpha vbeta 3 integrin MoAb and RGD peptide as well as soluble CD31 inhibited endothelial CD31-induced enhancement of eosinophil adhesion to IL-4-stimulated HUVECs. However, anti-alpha vbeta 3 integrin MoAb had no significant inhibitory effect on the eosinophil adhesion to IL-4-stimulated or unstimulated HUVECs without CD31 stimulation of HUVECs. Finally, CD31 stimulation of eosinophils increased the adhesive function of alpha 4beta 1 integrin (VLA-4) to its ligand fibronectin and their adhesion to IL-4-stimulated HUVECs in a VLA-4-dependent manner. These results indicate that CD31-mediated inside-out signaling activates alpha vbeta 3 integrin on endothelial cells, that the heterophilic alpha vbeta 3 integrin/CD31 interaction induces beta 1 integrin-mediated adhesion of eosinophils to endothelial cells, and that the heterophilic interaction itself is not significantly involved in firm adhesion of eosinophils to endothelial cells.


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