The role of PECAM-1 (CD31) in leukocyte emigration: studies in vitro and in vivo

Abstract

Platelet/endothelial cell adhesion molecule-1 (PECAM-1, CD31) is a molecule capable of mediating both homophilic and heterophilic adhesion. It is constitutively expressed and concentrated in the lateral borders between endothelial cells and expressed on the surfaces of neutrophils, monocytes, and some T cell subsets, as well as on platelets. In a quantitative in vitro assay, monoclonal antibody against PECAM-1 or soluble recombinant PECAM-1 selectively blocked passage of both neutrophils and monocytes across the endothelial monolayer by 70-90% without interfering with the ability of these cells to bind to the apical endothelial cell surface. These regents worked whether directed against leukocyte PECAM-1 or against endothelial cell PECAM-1 and were not additive, suggesting that a homophilic interaction was occurring. In a murine model of acute inflammation, thioglycollate-induced peritonitis, a monoclonal antibody against mouse PECAM-1 blocked emigration of leukocytes into the peritoneal cavity down to background levels. Examination of peritoneal venules in these mice revealed many leukocytes in apparent contact with the endothelial surface but unable to cross the intima. Thus, PECAM-1 has a distinct role in the transendothelial migration phase of leukocyte emigration, independent of the adhesion events on the apical surface.