NEUTROPHIL ADHESION TO HUMAN ENDOTHELIAL-CELLS IS INDUCED BY THE MEMBRANE ATTACK COMPLEX - THE ROLES OF P-SELECTIN AND PLATELET-ACTIVATING-FACTOR

A variety of inflammatory diseases are accompanied by activation of th e complement system. We examined the role of the membrane attack compl ex (MAC) in mediating neutrophil adhesion to endothelial cells. To ass emble the MAC in endothelial cell monolayers, a C5b-like molecule was created through the treatment of purified C5 with the oxidizing agent chloramine-T, followed by addition of the remaining components (C6-C9) that constitute the MAC. Use of this method abrogated potentially con founding effects mediated by other complement components (e.g., C5a). MAC assembly resulted in a rapid (30 min), concentration-dependent inc rease in neutrophil adherence. A monoclonal antibody directed against P-selectin inhibited MAC-mediated neutrophil adhesion. A whole cell EI A confirmed P-selectin expression after formation of the MAC. Incubati on of neutrophils with the platelet-activating factor receptor antagon ist, CF 3988, also significantly decreased adhesion, indicating that P AF plays a role in MAC-mediated adhesion. These results suggest that t he MAC can promote neutrophil adhesion through P-selectin and PAF-medi ated mechanisms.