CONTRIBUTION OF PLASMINOGEN-ACTIVATOR UROKINASE TO IN-VITRO CYTOTOXICITY OF DIPHTHERIA-TOXIN

Nicking of diphtheria toxin (DT), i.e. proteolytic cleavage at an argi nine-rich region within the first disulphide loop, is a prerequisite t o the intoxication process. We show that protease(s) required in this process was synthesized and secreted by the sensitive cells and that a ntibodies against plasminogen activator urokinase (uPA) decreased the in vitro cytotoxicity of DT on Vero cells. Our results demonstrate tha t uPA secreted by Vero cells cultured in vitro is one of the cellular proteases involved in the cleavage and activation of diphtheria toxin.