Inhibition of the activation of Hageman factor (factor XII) by complement subcomponent C1q

• Published in: The Journal of clinical investigation Vol. 80; no. 2; pp. 516 - 521
• Main Authors: REHMUS, E. H, GREENE, B. M, EVERSON, B. A, RATNOFF, O. D
• Format: Journal Article
• Language: English
• Published: Ann Arbor, MI American Society for Clinical Investigation 01-08-1987
• Subjects: Amides - metabolism; Antibodies, Monoclonal; Biological and medical sciences; Blood Coagulation; Blood coagulation. Blood cells; Coagulation factors; Complement Activating Enzymes - metabolism; Complement C1 - metabolism; Complement C1q; Ellagic Acid - antagonists & inhibitors; Factor XII - antagonists & inhibitors; Fundamental and applied biological sciences. Psychology; Glass; Humans; Microbial Collagenase; Molecular and cellular biology; Blood coagulation; Fixation; Inhibition; Complement C1q; Factor XII; Coagulation factor
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI113100

Hageman factor (HF, Factor XII) is activated by glass, collagen, and ellagic acid, and initiates blood coagulation via the intrinsic pathway. C1q inhibits collagen-induced platelet aggregation and adherence of platelets to glass, effects attributable to the collagen-like region of C1q. We examined the actions of C1q on HF activation. Incubation of C1q with HF before addition of HF-deficient plasma extended the activated partial thromboplastin time. Similarly, when glass tubes were coated with C1q before testing, the partial thromboplastin time of normal plasma was increased. C1q reduced the activation of HF by ellagic acid, as measured by the release of p-nitroaniline from the synthetic substrate H-D-prolyl-L-phenylalanyl-L-arginine-p-nitroanilide dihydrochloride, an effect inhibited by monoclonal anti-human C1q murine IgG and by digestion of C1q by collagenase. Thus, C1q inhibits activation of HF in vitro in clot-promoting and amidolytic assays and suggests a regulatory mechanism for the inhibition of coagulation.