PECAM-1 IS REQUIRED FOR TRANSENDOTHELIAL MIGRATION OF LEUKOCYTES

Platelet/endothelial cell adhesion molecule 1 (PECAM-1; CD31) is cruci al to the process of leukocyte transmigration through intercellular ju nctions of vascular endothelial cells. A monoclonal antibody to PECAM, or recombinant soluble PECAM, blocks transendothelial migration of mo nocytes 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 recombina nt PECAM again block transmigration of both monocytes and neutrophils. Anti-PECAM does not block chemotaxis of either cell type. Light and e lectron microscopy reveal that leukocytes blocked in transmigration re main tightly bound to the apical surface of the endothelial cell, prec isely over the intercellular junction. Thus, the process of leukocyte emigration can be dissected into three successive stages: rolling, med iated by the selectin class of adhesion molecules; tight adhesion, med iated by the leukocyte integrins and their endothelial cell counter-re ceptors; and now transmigration, which, based on these studies, requir es PECAM-1.