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Four fungal metabolites, chaetoglobosin A (CGA), crinipellin B (CPB), geodin (GE) and triticone B (TTB), were found to enhance fibrinolytic activity of bovine aortic endothelial cells. Plasmin generation on the cells was elevated 2- to 4-fold when treated with these agents at a concentration of 3 approximately 100 microM. These effects were dependent on plasminogen and inhibited by anti-urokinase antibody. The effect of CGA, but not of CPB, GE and TTB, was abolished by cycloheximide. In a cell-free system, plasmin and urokinase activities as well as urokinase-catalyzed plasminogen activation were not enhanced by these agents. CGA, but not others, induced the production of urokinase in endothelial cells. CPB and GE accelerated plasminogen activator inhibitor- 1 (PAI-1) inactivation, and TTB caused direct, reversible inhibition of PAI-1. Thus, induction of urokinase by CGA and inhibition of PAI-1 by CPB, GE and TTB may, at least partly, account for the elevation of fibrinolytic activity of endothelial cells.

Enhancement of Fibrinolytic Activity of Vascular Endothelial Cells by Chaetoglobosin A, Crinipellin B, Geodin and Triticone B.