Expression of the catalytic activity of plasminogen activator under physiologic conditions.
We have investigated the factors governing the plasminogen-dependent fibrinolysis catalyzed by the serine proteinase, plasminogen activator (EC 3.4.21.-), under physiologic conditions. We found that live rabbit fibroblasts digested much less fibrin than predicted by cell-free assay of the secreted plasminogen activator. The reduced catalytic activity of plasminogen activator expressed by cells growing on fibrin was regulated by the salt concentration of culture medium. The plasminogen activators of cells from several mammalian species were inhibited by physiologic salt concentrations (0.15 M NaCl) in cell-free assays. CaCl2 and KCl, but not D-glucose, were also effective inhibitors. The catalytic activity of purified human urokinase and of plasmin was unaffected by increased ionic strength. Plasminogen activators secreted both spontaneously and in response to stimulation by the tumor promoter, 12-O-tetradecanoyl-phorbol-13-acetate, were inhibited by 0.15 M NaCl. Physiologic salt concentration appeared to function by interacting with plasminogen activator, or plasminogen, and a third component, possibly a reversible inhibitor. One consequence of this regulation of plasminogen activator under physiologic conditions is the limitation of plasminogen-dependent fibrin degradation by living cells.
D000818:Animals; D002384:Catalysis; D002478:Cells, Cultured; D002712:Chlorides / Q000494:pharmacology*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D005341:Fibrinolysin / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D010960:Plasminogen Activators / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015849:Plasminogen Inactivators; D011817:Rabbits; D012965:Sodium Chloride / Q000008:administration & dosage; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D002712:Chlorides; D015849:Plasminogen Inactivators; D012965:Sodium Chloride; D010960:Plasminogen Activators; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator