Inhibition of neutrophil activation by fibrinogen.
Physiological levels of human fibrinogen markedly inhibited the chemotactic activity of human neutrophils triggered by zymosan-activated serum (ZAS), C5a, or IL-8 in a Boyden chamber assay. Fibrinogen also slightly inhibited the N-formyl-methionyl leucyl-phenylalanine (FMLP)-induced migration of human neutrophils. Albumin was devoid of the inhibitory activities displayed by fibrinogen in this system. The inhibition of chemotaxis by fibrinogen was dose-dependent and saturable. Fibrinogen placed in the upper compartment of the Boyden chamber produced a larger 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, both arginine and glutamine failed to suppress the fibrinogen-mediated inhibition of neutrophil chemotaxis. AHA counteracts the inhibition of ZAS-induced chemotaxis by anti-CD18 monoclonal antibody, suggesting that lysine binding sites are required for integrin function in chemotaxis. Fibrinogen also inhibited, in a dose-dependent manner, the oxygen consumption of neutrophils activated by opsonized zymosan. Taken together, the present results indicate that fibrinogen modulates neutrophil functions and suggest that in addition to its role in blood coagulation, circulating fibrinogen may be involved in regulation of the inflammatory response.
Department of Clinical Biochemistry, Hadassah University Hospital Mount Scopus, Jerusalem, Israel.
A A
AA
Higazi
I I
II
Barghouti
S K
SK
Ayesh
M
M
Mayer
Y
Y
Matzner
D000596:Amino Acids / Q000494:pharmacology; D015119:Aminocaproic Acid / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018821:CD18 Antigens / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D015936:Complement C5a / Q000037:antagonists & inhibitors; D005340:Fibrinogen / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation; D016209:Interleukin-8 / Q000037:antagonists & inhibitors; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000037:antagonists & inhibitors; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects*; D016897:Respiratory Burst / Q000187:drug effects*; D012709:Serum Albumin / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology
D000596:Amino Acids; D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D016209:Interleukin-8; D012709:Serum Albumin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015936:Complement C5a; D005340:Fibrinogen; D015054:Zymosan; D015119:Aminocaproic Acid