title: Ligation of CD31 (PECAM-1) on endothelial cells increases adhesive function of alphavbeta3 integrin and enhances beta1 integrin-mediated adhesion of eosinophils to endothelial cells.
abstract: We determined the role of the heterophilic interaction of alphavbeta3 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 alphavbeta3 integrin to its ligand RGD peptide, the binding of which reached a maximum at 10 minutes after the stimulation, and the CD31-induced alphavbeta3 integrin activation on HUVECs was inhibited by inhibitors of protein kinase C and phosphatidylinositol 3 kinase (PI3-kinase). Furthermore, anti-alphavbeta3 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-alphavbeta3 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 alpha4beta1 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 alphavbeta3 integrin on endothelial cells, that the heterophilic alphavbeta3 integrin/CD31 interaction induces beta1 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.
authors.affiliation: Department of Medicine II, Chiba University School of Medicine, Chiba, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Chiba
authors.forename: N
authors.initials: N
authors.lastname: Nakagawa
authors.forename: K
authors.initials: K
authors.lastname: Kurasawa
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Y
authors.initials: Y
authors.lastname: Saito
authors.forename: I
authors.initials: I
authors.lastname: Iwamoto
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002450:Cell Communication / Q000502:physiology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D004804:Eosinophils / Q000166:cytology / Q000502:physiology*; D006801:Humans; D019012:Integrin beta1 / Q000502:physiology*; D015847:Interleukin-4 / Q000494:pharmacology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000502:physiology*; D019030:Receptors, Vitronectin / Q000502:physiology*
chemical_list: D000911:Antibodies, Monoclonal; D019012:Integrin beta1; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019030:Receptors, Vitronectin; D015847:Interleukin-4