CD31/PECAM-1 is a ligand for alpha v beta 3 integrin involved in adhesion of leukocytes to endothelium.

Abstract

Abstract. To protect the body efficiently from infectious organisms, leukocytes circulate as nonadherent cells in the blood and lymph, and migrate as adherent cells into tissues. Circulating leukocytes in the blood have first to adhere to and then to cross the endothelial lining. CD31/PECAM-1 is an adhesion molecule expressed by vascular endothelial cells, platelets, monocytes, neutrophils, and naive T lymphocytes. It is a transmembrane glycoprotein of the immunoglobulin gene superfamily (IgSF), with six Ig-like homology units mediating leukocyte-endothelial interactions. The adhesive interactions mediated by CD31 are complex and include homophilic (CD31-CD31) or heterophilic (CD31-X) contacts. Soluble, recombinant forms of CD31 allowed us to study the heterophilic interactions in leukocyte adhesion assays. We show that the adhesion molecule otv[33 integrin is a ligand for CD31. The leukocytes revealed adhesion mediated by the second Ig-like domain of CD31, and this binding was inhibited by av[33 integrin-specific antibodies. Moreover Otv~ 3 was precipitated by recombinant CD31 from cell lysates. These data establish a third IgSF-integrin pair of adhesion molecules, CD31-otvI33 in addition to VCAM-1, MadCAM-1/ot4 integrins, and ICAM/B2 integrins, which are major components mediating leukocyteendothelial adhesion. Identification of a further versatile adhesion pair broadens our current understanding of leukocyte-endothelial interactions and may provide the basis for the treatment of inflammatory disorders and metastasis formation.

Modulation of Expression of Endothelial Intercellular Adhesion Molecule-1, Platelet–Endothelial Cell Adhesion Molecule-1, and Vascular Cell Adhesion Molecule-1 in Aortic Arch Lesions of Apolipoprotein E–Deficient Compared With Wild-Type Mice

“…36 In addition, it has been suggested that PECAM-1 can interact with upregulated ␣ v ␤ 3 . 37,38 In the present study, a significant modulation of endothelial PECAM-1 expression, lining the whole vessel wall circumference, was observed for apoEdeficient but not wild-type mice. It is of interest to note that PECAM-1 expression can be significantly modulated after treatment of human umbilical vein endothelial cells with inflammatory cytokines.…”

Human aging and CD31+T-cell number, migration, apoptotic susceptibility, and telomere length

“…The unique structural homology of CD31's extracellular region is responsible for facilitating numerous heterophilic and homophilic binding interactions between differing vascular tissues (10,16). For example, CD31 is highly expressed in the border junctions of endothelial cells where it plays a role in endothelial cell motility and regulating leukocyte transendothelial migration (31). In CD31 knockout mice, endothelial cell motility and filopodia formation as well as neovascularization are markedly impaired (5).…”

Induction of Hyporesponsiveness and Impaired T Lymphocyte Activation by the CD31 Receptor:Ligand Pathway in T Cells

“…Apart from the T cell CD31 ligand (T-CD31L; Ref. 13), the proposed heterophilic counterreceptors of CD31 include a heparin-containing proteoglycan (16,17), the integrin ␣ v ␤ 3 (18,19), a molecule expressed by parasitized RBC (20), and the ADP-ribosyl cyclase CD38 (21).…”