title: 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 Ca(2+). Fibrin, which is proteolytically produced from fibrinogen by thrombin, binds to the same sugar residues as fibrinogen in the presence of 5 mM Ca(2+), while it markedly binds to N-acetylneuraminic acid in the absence of Ca(2+). Thrombin-induced fibrin polymerization was monitored by turbidity at 350 nm. In the presence of Ca(2+), Man and sugars having N-acetyl groups were found to inhibit the increase in turbidity, but only Man inhibited it in the absence of Ca(2+). 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.
authors.affiliation: Graduate School of Humanities and Sciences and Glycoscience Institute, Ochanomizu University, 2-1-1 Ohtsuka, Bunkyo-ku, Tokyo, 112-8610, Japan.
authors.forename: Kimie
authors.initials: K
authors.lastname: Date
authors.forename: Mami
authors.initials: M
authors.lastname: Ohyama
authors.forename: Haruko
authors.initials: H
authors.lastname: Ogawa
mesh_terms: D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002241:Carbohydrates / Q000737:chemistry; D002417:Cattle; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D005337:Fibrin / Q000378:metabolism* / Q000648:ultrastructure; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D058105:Polymerization / Q000187:drug effects; D011485:Protein Binding; D013917:Thrombin / Q000494:pharmacology
chemical_list: D002241:Carbohydrates; D003432:Cross-Linking Reagents; D004533:Egtazic Acid; D005337:Fibrin; D005340:Fibrinogen; D013917:Thrombin; D002118:Calcium