Monoclonal antibodies inhibitory to human plasmin. Definitive demonstration of a role for plasmin in activating the proenzyme of urokinase-type plasminogen activator.
Four monoclonal antibodies raised against purified human plasminogen were characterized for their effects on the activation of plasminogen and on three enzymic properties of plasmin: (a) thioesterolysis, (b) fibrinolysis, (c) conversion of high-Mr urokinase to its low-Mr form. None of the monoclonal antibodies inhibited plasminogen (plg) activation by urokinase. The monoclonal antibodies characterized in this study fell into three groups. Anti-plg 1 inhibited (a), (b) and (c), while anti-plg 2 inhibited activities (a), (b) and (c) to varying degrees but also formed complexes with plasmin that were stable to sodium dodecyl sulphate. Anti-plg 3 and anti-plg 4 inhibited only activity (c). Selective use of these monoclonal antibodies demonstrated unequivocally that plasmin mediates the activation of the proenzyme form of urokinase-type plasminogen activator. Besides their use in affinity chromatography, therefore, these antibodies are valuable for defining the role of plasmin in the mechanisms of extracellular matrix degradation.
D000911:Antibodies, Monoclonal / Q000276:immunology*; D002846:Chromatography, Affinity; D003110:Colonic Neoplasms / Q000201:enzymology; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000032:analysis*; D005341:Fibrinolysin / Q000502:physiology*; D005342:Fibrinolysis; D006801:Humans; D008970:Molecular Weight; D010958:Plasminogen / Q000276:immunology* / Q000302:isolation & purification; D010960:Plasminogen Activators / Q000032:analysis*; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis* / Q000378:metabolism / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D004792:Enzyme Precursors; D010958:Plasminogen; D010960:Plasminogen Activators; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator