A unique property of a plasma proteoglycan, the C1q inhibitor. An anticoagulant state resulting from its binding to fibrinogen.
The C1q inhibitor, C1qI, an approximately 30-kD circulating chondroitin-4 sulfate proteoglycan, displayed concentration-dependent prolongation of plasma and fibrinogen solution clotting times. Under factor XIIIa catalyzed cross-linking conditions and maximum C1qI concentrations, minor amounts of clot formed displaying complete gamma-gamma dimer formation but virtually no alpha-polymer formation. The anticoagulant effect was undiminished by its binding to C1q, by increased ionic strength, and by CaCl2, but was abolished by incubation of C1qI with chondroitinase ABC. 125I-labeled C1qI bound to immobilized fibrinogen, fibrin monomer, fibrinogen plasmic fragments D1 and E, and fibrin polymers. Occupancy on the E domain required uncleaved fibrinopeptides together with another structure(s), and it did not decrease binding of thrombin to fibrinogen. Occupancy on the D domain did not decrease the fibrinogen binding to fibrin monomer. We conclude that the E domain occupancy impaired fibrinopeptide cleavage, and occupancy on the D domain impaired polymerization, both steric hindrance effects. C1qI binding to fibrinogen explains at least in part the well-known fibrin(ogen) presence in immune complex-related lesions, and the fibrinogen presence in vascular basement membranes and atheromata. We postulate that fibrin binding by resident basement membrane proteoglycans provides dense anchoring of thrombus, substantially enhancing its hemostatic function.
Galanakis
D K
DK
Blood Bank, University Hospital, State University of New York, Stony Brook 11794.
Ghebrehiwet
B
B
D000925:Anticoagulants / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D011508:Chondroitin Sulfate Proteoglycans / Q000097:blood* / Q000302:isolation & purification / Q000494:pharmacology; D002846:Chromatography, Affinity; D015922:Complement C1q / Q000378:metabolism; D005337:Fibrin / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism*; D005344:Fibrinopeptide A / Q000378:metabolism; D005345:Fibrinopeptide B / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D011485:Protein Binding
D000925:Anticoagulants; D011508:Chondroitin Sulfate Proteoglycans; D005344:Fibrinopeptide A; D005345:Fibrinopeptide B; D015922:Complement C1q; D005337:Fibrin; D005340:Fibrinogen