title: Enhancement of plasminogen binding to U937 cells and fibrin by complestatin.
abstract: Plasminogen binds to endothelial and blood cells as well as to fibrin, where the zymogen is efficiently activated and protected from inhibition by alpha 2-antiplasmin. In the present study we have found that complestatin, a peptide-like metabolite of a streptomyces, enhances binding of plasminogen to cells and fibrin. Complestatin, at concentrations ranging from 1 to 5 microM, doubled 125I-plasminogen binding to U937 cells both in the absence and presence of lipoprotein(a), a putative physiological competitor of plasminogen. The binding of 125I-plasminogen in the presence of complestatin was abolished by epsilon-aminocaproic acid, suggesting that the lysine binding site(s) of the plasminogen molecule are involved in the binding. Equilibrium binding analyses indicated that complestatin increased the maximum binding of 125I-plasminogen to U937 cells without affecting the binding affinity. Complestatin was also effective in increasing 125I-plasminogen binding to fibrin, causing 2-fold elevation of the binding at approximately 1 microM. Along with the potentiation of plasminogen binding, complestatin enhanced plasmin formation, and thereby increased fibrinolysis. These results would provide a biochemical basis for a pharmacological stimulation of endogenous fibrinolysis through a promotion of plasminogen binding to cells and fibrin.
authors.affiliation: Department of Applied Biological Science, Tokyo Noko University, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Tachikawa
authors.forename: K
authors.initials: K
authors.lastname: Hasumi
authors.forename: A
authors.initials: A
authors.lastname: Endo
mesh_terms: D002460:Cell Line; D002733:Chlorophenols / Q000494:pharmacology*; D003169:Complement Inactivator Proteins / Q000494:pharmacology*; D005337:Fibrin / Q000378:metabolism*; D006801:Humans; D009000:Monocytes / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology*; D010456:Peptides, Cyclic; D010958:Plasminogen / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects
chemical_list: D002733:Chlorophenols; D003169:Complement Inactivator Proteins; D009842:Oligopeptides; D010456:Peptides, Cyclic; C023490:complestatin; D005337:Fibrin; D010958:Plasminogen