ROLES OF PLATELET ENDOTHELIAL-CELL ADHESION MOLECULE-1 (PECAM-1,CD31)IN NATURAL-KILLER-CELL TRANSENDOTHELIAL MIGRATION AND BETA(2) INTEGRIN ACTIVATION

Platelet/endothelial cell adhesion molecule-1 (PECAM-1, CD31) is a gly coprotein expressed on the surfaces of monocytes, neutrophils, platele ts, a subpopulation of T cells, and, as described in this work, on NK cells. It is also concentrated at the junctions between endothelial ce lls (EC) in culture, and is expressed on continuous endothelia in all tissues. PECAM has been shown to be involved in monocyte and neutrophi l transendothelial migration in vitro and in vivo. The function of PEC AM in NK cell interaction with EC has never been studied, In this work , we demonstrate that ligation of PECAM on the surface of NK cells act ivates their beta(2) integrins. Anti-PECAM Abs added to NK cells cause d a 2.5- to 4-fold increase in the binding of these cells to monolayer s of EC or 3T3 cells transfected with ICAM-1, and this was inhibited b y a mAb against CD18, PECAM also plays a role in NK cell transendothel ial migration. Anti-PECAM Abs inhibited 50% of NK cell transmigration through resting EC in an in vitro system. The transmigration of CD56(d im) and CD56(bright) cells was inhibited equally. IFN-gamma increased NK cell transmigration; the transmigration of CD56(bright) cells was i ncreased to a much greater extent than CD56(dim) transmigration (4-fol d vs 1.5-fold), Anti-PECAM inhibited the transmigration of CD56(dim) c ells by 30%, while that of CD56(bright) cells was not blocked. These s tudies demonstrate that PECAM-1 could play an important role in the ex travasation of NK cells into tissues for constitutive surveillance and into sites of inflammation.