Fas activation reduces neutrophil adhesion to endothelial cells

Polymorphonuclear neutrophils (PMN) express apoptotic markers and lose effe ctor functions including adhesion, chemotaxis, and phagocytosis when cultur ed overnight. although the loss of function correlates with apoptosis, it i s not clear if functions are lost before an early marker of apoptosis, the display of phosphatidylserine (PS), targets PMN for removal by phagocytic c ells. To address this question, freshly isolated PMN were treated with Fas- activating antibodies to induce apoptosis rapidly. Early markers of apoptos is and PMA-stimulated adhesion to endothelial cells were measured. After 1 h of Fas exposure, only 16% PMN had externalized PS. In contrast, Fas activ ation reduced PMA-stimulated adhesion between 68 and 27% depending on PMA c oncentration. The loss of adhesion was accompanied by a reduction in beta2 integrin expression and receptor clustering. These results indicate that th e Fas-induced loss of adhesion may precede PS externalization and could lim it participation in the inflammatory response before PS externalization tar gets PMN for removal.