NEUTROPHIL PLATELET ENDOTHELIAL-CELL ADHESION MOLECULE-1 PARTICIPATESIN NEUTROPHIL RECRUITMENT AT INFLAMMATORY SITES AND IS DOWN-REGULATEDAFTER LEUKOCYTE EXTRAVASATION

Platelet endothelial cell adhesion molecule-1 (PECAM-1), a member of t he Ig superfamily, is found on endothelial cells and neutrophils, and has been shown to be involved in the migration of leukocytes across th e endothelium. Although studies have supported a role for endothelial PECAM-1 in this process, the participation of neutrophil PECAM-1 in vi vo has not been unambiguously demonstrated. Therefore, to examine the involvement of neutrophil PECAM-1 in leukocyte recruitment, we studied the effect of a blocking Ab against murine PECAM-1 on neutrophil recr uitment in on established model of murine peritonitis and in a murine model for studying leukocyte-endothelial interactions involving the hu man vasculature. These studies not only confirmed that neutrophil PECA M-1 is important in the accumulation of neutrophils at inflammatory si tes, but that extravasated neutrophils displayed decreased surface exp ression of PECAM-1. In vitro, the surface expression of murine neutrop hil PECAM-1 was not decreased significantly by inflammatory mediators, but was reduced after transendothelial migration. These studies, cons istent with previous in vitro observations, confirm that neutrophil PE CAM-1, as well as endothelial PECAM-1, is involved in the recruitment of neutrophils into inflammatory sites in vivo, and suggest that the e xpression of neutrophil PECAM-1 is down-regulated after extravasation into inflamed tissues possibly as a result of engagement of its ligand .