C1q component of complement binds to fibrinogen and fibrin

Abstract

The interaction of complement component C1 q with fibrinogen and fibrin was studied by using a solid-phase direct binding assay. Scatchard analysis of radiodinated fibrinogen binding to C1q indicated at least two high-affinity binding constants (Kd) calculated as 8.5 and 120 nM. In contrast, binding of radiodionated fibrin to C1q showed only a single class of binding sites with a calculated Kd of 600 nM. Fibrinogen-C1q binding was shown to decrease as a function of increasing salt concentrations, indicating either the presence of charged amino acids in the binding sites or an ionic strength induced conformational dependency of the binding. In direct binding studies using isolated fragments of C1q, both the collagen-like domain of C1q and the globular domains of C1q were shown to bind fibrinogen, indicating at least one binding site for fibrinogen is located in each of the major domains of C1q. Addition of the thrombin-generated peptides of fibrinogen, fibrinopeptides A and B, enhanced C1q-fibrinogen binding, again indicating a complex binding interaction. These results indicate that C1q and fibrinogen are capable of high-affinity interactions that may serve to sequester these complexes in areas of tumors, immune complex deposition, or wounds.