Enhancement of fibrinolytic activity of U937 cells by malformin A1.

We have found that malformin A1, a cyclopentapeptide metabolite of Aspergillus niger, enhanced 2.0- to 3.2-fold the 125I-fibrin clot lysis when incubated at 1 to approximately 10 microM with both U937 cells and blood plasma, both of which were essential to the malformin A1 action. The effect was inhibited by epsilon-aminocaproic acid and anti-urokinase serum, but not by anti-tissue-type plasminogen activator IgG, showing that the enhancement was mediated by urokinase-catalyzed plasminogen activation. However, malformin A1 affected neither cellular urokinase activity nor cell-free reactions involved in the fibrinolytic pathway. Malformin-treated, washed cell had an increased capacity to degrade fibrin in the presence of plasma. These results suggest that malformin A1 enhances fibrinolytic activity by affecting cell-mediated response to initiate and/or propagate fibrinolytic activity.