A UNIQUE PROPERTY OF A PLASMA PROTEOGLYCAN, THE C1Q INHIBITOR - AN ANTICOAGULANT STATE RESULTING FROM ITS BINDING TO FIBRINOGEN

The C1q inhibitor, C1qI, an similar to 30-kD circulating chondroitin-4 sulfate proteoglycan, displayed concentration-dependent prolongation of plasma and fibrinogen solution clotting times. Under factor XIIIa c atalyzed cross-linking conditions and maximum C1qI concentrations, min or amounts of clot formed displaying complete gamma-gamma dimer format ion 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 chondroitin ase ABC. I-125-labeled C1qI bound to immobilized fibrinogen, fibrin mo nomer, fibrinogen plasmic fragments D-1 and E, and fibrin polymers. Oc cupancy on the E domain required uncleaved fibrinopeptides together wi th another structure(s), and it did not decrease binding of thrombin t o fibrinogen. Occupancy on the D domain did not decrease the fibrinoge n binding to fibrin monomer. We conclude that the E domain occupancy i mpaired fibrinopeptide cleavage, and occupancy on the D domain impaire d polymerization, both steric hindrance effects. C1qI binding to fibri nogen explains at least in part the well-known fibrin(ogen) presence i n immune complex-related lesions, and the fibrinogen presence in vascu lar basement membranes and atheromata. We postulate that fibrin bindin g by resident basement membrane proteoglycans provides dense anchoring of thrombus, substantially enhancing its hemostatic function.