LIGATION OF CD31 PECAM-1 MODULATES THE FUNCTION OF LYMPHOCYTES, MONOCYTES AND NEUTROPHILS/

CD31 or platelet/endothelial cell adhesion molecule (PECAM-1) is a 130 -kDa glycoprotein expressed on endothelial cells, granulocytes, a subs et of lymphocytes and platelets. In this study we examined the ability of four monoclonal antibodies (mAb) against different domains of CD31 to modulate the function of T lymphocytes, monocytes and neutrophils. Engagement of CD31 On T lymphocytes results in co-stimulation of T ly mphocyte proliferation to suboptimal doses of anti-CD31 mAb. This prol iferation is accompanied by secretion of numerous cytokines and chemok ines, up-regulation of CD25 and an increase in cell size. Purification of T lymphocytes into CD45RO and CD45RA subsets showed that only naiv e CD45RA T lymphocytes are co-stimulated by anti-CD31 mAb. Further stu dies on neutrophils show that engagement of CD31 results in down-regul ation of CD62L and up-regulation of CD11b/CD18 as well as oxidative bu rst, as assessed by superoxide release. In addition, ligation of CD31 on monocytes results in TNF-alpha secretion, and studies with various cell signaling inhibitors indicate that tyrosine kinases and cAMP-depe ndent kinases are involved in monocyte activation via CD31. Of the fou r mAb used in this study, only two activated human leukocytes. These m Ab were PECAM-1.3 and hec7, which bind to domains 1 and 2 of CD31. We conclude that engagement of domains 1 and 2 of CD31 results in outside -in signaling in leukocytes.