PECAM-1 is required for transendothelial migration of leukocytes.

Abstract

SummaryPlatelet/endothelial cell adhesion molecule 1 (PECAM-1; CD31) is crucial to the process of leukocyte transmigration through intercellular junctions of vascular endothelial cells. A monoclonal antibody to PECAM, or recombinant soluble PECAM, blocks transendothelial migration of monocytes by 70-90%. Pretreating either the monocytes or the endothelial junctions with antibody blocks transmigration. If the endothelium is first activated by cytokines, anti-PECAM antibody or soluble recombinant PECAM again block transmigration of both monocytes and neutrophils. Anti-PECAM does not block chemotaxis of either cell type. Light and electron microscopy reveal that leukocytes blocked in transmigration remain tightly bound to the apical surface of the endothelial cell, precisely over the intercellular junction. Thus, the process of leukocyte emigration can be dissected into three successive stages: rolling, mediated by the selectin dass of adhesion molecules; tight adhesion, mediated by the leukocyte integrins and their endothelial cell counter-receptors; and now transmigration, which, based on these studies, requires PECAM-1.

Effects of pulse methylprednisolone on cell adhesion molecules in the synovial membrane in rheumatoid arthritis. Reduced E‐selectin and intercellular adhesion molecule 1 expression

“…First, a report by Oda and Katori (61) (using the model of leukocyte flow in a hamster cheek pouch) suggested that glucocorticoids did not affect leukocyte rolling or firm adhesion to the endothelium, but rather, they affected the later stages of transmigration, which are at least partially mediated by PECAM (11). Second, interfering with PECAM function inhibits neutrophil trafficking in animal models of inflammation (11,62). Third, TNFa treatment has been reported to cause redistribution of PECAM on vascular endothelium to intercellular junctions (19), and we had previously found reduced TNFa levels after MP treatment (35).…”

CD99 Is a Key Mediator of the Transendothelial Migration of Neutrophils

“…Anti-PECAM blocking reagents have been demonstrated to block the transmigration of monocytes (14), neutrophils (14, 18 -20), NK cells (21), and eosinophils (22). A recent study using an in vitro model of inflammation described the involvement of CD99, a heavily glycosylated 32-kDa transmembrane protein, as a second molecule in the transmigration of monocytes across EC borders (23).…”

Leucine125Valine (Leu125Val) Gene Polymorphism of Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1) and Myocardial Infarction in Indian Population

“…Platelet endothelial cell adhesion (PECAM-1) is of the immunoglobulin (Ig)-superfamily with wide variety of functions in platelet activation, inflammation, cell survival and the immune response and involved in transendothelial migration of monocytes (TEM) [1][2][3][4]. Thus it has a role in atherosclerotic plaque formation.…”

“…It has 6 Ig-like extracellular domains (encoded by exon 3-8) a short trans-membrane domain (encoded by exon 9) and a short cytoplasmic tail (encoded by exon [10][11][12][13][14][15][16] [6,7]. The importance of the first domain of PECAM-1 (encoded by exon 3) is underscored since PECAM-1 forms homophilic binding via its 1st or 1st plus 2nd extracellular Ig-like domains or heterophilic binding with other molecules to mediate cell-cell adhesion [3,8]. A Mutation in PECAM-1 gene in Exon-3 has been identified that involves a base pair substitution (C?G) at position ?373 causing Leucine (Leu) to Valine (Val) substitution at amino acid position 125 (rs668) [9].…”

“…A Mutation in PECAM-1 gene in Exon-3 has been identified that involves a base pair substitution (C?G) at position ?373 causing Leucine (Leu) to Valine (Val) substitution at amino acid position 125 (rs668) [9]. Since the interaction or activation of PECAM-1 is mainly via homophilic binding with its 1st extracellular Ig-like domains [3,8], this polymorphism might affect the homophilic binding capability and influence individual susceptibility to coronary artery disease (CAD).…”