INHIBITION OF NEUTROPHIL ACTIVATION BY FIBRINOGEN

Physiological levels of human fibrinogen markedly inhibited the chemot actic activity of human neutrophils triggered by zymosan-activated ser um (ZAS), C5a, or IL-8 in a Boyden chamber assay. Fibrinogen also slig htly inhibited the N-formyl-methionyl leucyl-phenylalanine (FMLP)-indu ced migration of human neutrophils. Albumin was devoid of the inhibito ry activities displayed by fibrinogen in this system, The inhibition o f chemotaxis by fibrinogen was dose-dependent and saturable. Fibrinoge n placed in the upper compartment of the Boyden chamber produced a lar ger inhibition than that obtained with fibrinogen placed in the lower compartment. Lysine as well as the lysine analog 6-aminohexanoic acid (AHA) decreased the inhibitory capacity of fibrinogen. In contrast, bo th arginine and glutamine failed to suppress the fibrinogen-mediated i nhibition of neutrophil chemotaxis. AHA counteracts the inhibition of ZAS-induced chemotaxis by anti-CD18 monoclonal antibody, suggesting th at lysine binding sites are required for integrin function in chemotax is. Fibrinogen also inhibited, in a dose-dependent manner, the oxygen consumption of neutrophils activated by opsonized zymosan. Taken toget her, the present results indicate that fibrinogen modulates neutrophil functions and suggest that in addition to its role in blood coagulati on, circulating fibrinogen may be involved in regulation of the inflam matory response.