Carbohydrate-binding activities of coagulation factors fibrinogen and fibrin

Abstract

The coagulation factors fibrinogen and fibrin play important roles in the final stage of the blood coagulation cascade. It has not been revealed whether fibrinogen has lectin activity or not. Here we demonstrate that fibrinogen and fibrin have carbohydrate-specific binding activities that inhibit fibrin clot formation. A solid-phase binding study using sugar-biotinyl polymer probes revealed that fibrinogen has the highest affinity to mannose (Man) in both the presence and absence of 5 mM Ca²⁺. Fibrin, which is proteolytically produced from fibrinogen by thrombin, binds to the same sugar residues as fibrinogen in the presence of 5 mM Ca²⁺, while it markedly binds to N-acetylneuraminic acid in the absence of Ca²⁺. Thrombin-induced fibrin polymerization was monitored by turbidity at 350 nm. In the presence of Ca²⁺, Man and sugars having N-acetyl groups were found to inhibit the increase in turbidity, but only Man inhibited it in the absence of Ca²⁺. Scanning electron microscopy observation of fibrin clots formed in the presence of various sugars showed that fibrin fibers formed in the presence of Man and N-acetyl group sugars were thinner and more branched. In contrast, thrombin has neither carbohydrate-binding activity nor is affected by sugars. These results suggest that carbohydrates and glycoconjugates may regulate fibrin clot formation in vivo.