Contribution of plasminogen activator urokinase to in vitro cytotoxicity of diphtheria toxin.
Nicking of diphtheria toxin (DT), i.e. proteolytic cleavage at an arginine-rich region within the first disulphide loop, is a prerequisite to the intoxication process. We show that protease(s) required in this process was synthesized and secreted by the sensitive cells and that antibodies against plasminogen activator urokinase (uPA) decreased the in vitro cytotoxicity of DT on Vero cells. Our results demonstrate that uPA secreted by Vero cells cultured in vitro is one of the cellular proteases involved in the cleavage and activation of diphtheria toxin.
Guidi-Rontani
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Unité des Toxines microbiennes, CNRS URA 18580, Institut Pasteur, Paris, France.
D000906:Antibodies / Q000276:immunology; D002460:Cell Line; D004247:DNA / Q000502:physiology; D004167:Diphtheria Toxin / Q000502:physiology*; D006801:Humans; D011480:Protease Inhibitors / Q000494:pharmacology; D011506:Proteins / Q000502:physiology; D014568:Urokinase-Type Plasminogen Activator / Q000276:immunology / Q000502:physiology*
D000906:Antibodies; D004167:Diphtheria Toxin; D011480:Protease Inhibitors; D011506:Proteins; D004247:DNA; D014568:Urokinase-Type Plasminogen Activator