title: Neutrophil adhesion to human endothelial cells is induced by the membrane attack complex: the roles of P-selectin and platelet activating factor.
abstract: A variety of inflammatory diseases are accompanied by activation of the complement system. We examined the role of the membrane attack complex (MAC) in mediating neutrophil adhesion to endothelial cells. To assemble 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 confounding effects mediated by other complement components (e.g., C5a). MAC assembly resulted in a rapid (30 min), concentration-dependent increase in neutrophil adherence. A monoclonal antibody directed against P-selectin inhibited MAC-mediated neutrophil adhesion. A whole cell EIA confirmed P-selectin expression after formation of the MAC. Incubation of neutrophils with the platelet-activating factor receptor antagonist, CF 3988, also significantly decreased adhesion, indicating that PAF plays a role in MAC-mediated adhesion. These results suggest that the MAC can promote neutrophil adhesion through P-selectin and PAF-mediated mechanisms.
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602, USA.
authors.forename: K S
authors.initials: KS
authors.lastname: Kilgore
authors.forename: P A
authors.initials: PA
authors.lastname: Ward
authors.forename: J S
authors.initials: JS
authors.lastname: Warren
mesh_terms: D002448:Cell Adhesion / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D009504:Neutrophils / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D019007:P-Selectin / Q000276:immunology / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000276:immunology / Q000378:metabolism*
chemical_list: D019007:P-Selectin; D010972:Platelet Activating Factor