Neutrophil collagenase activation: the role of oxidants and cathepsin G.
The events leading to neutrophil collagenase activation in vivo were analyzed using phorbol myristate acetate (PMA) stimulated neutrophil supernatant. Under the conditions when this supernatant was incubated with the serine proteinase inhibitor, phenylmethylsulfonyl fluoride (PMSF), and then treated with the oxidant, hypochlorous acid (HOCl), collagenase was activated. When cathepsin G, a known activator of neutrophil collagenase, was also present, less HOCl was required to activate the latent collagenase. These experiments support the conclusion that activation of neutrophil collagenase occurs in vivo by both an oxidant and an enzymatic mechanism where the effectiveness of oxidants is enhanced by cathepsin G.
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UMDNJ-Robert Wood Johnson Medical School, Biochemistry Department, Piscataway 08854.
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D056649:Cathepsin G; D002403:Cathepsins / Q000494:pharmacology*; D017364:Collagenases; D004789:Enzyme Activation / Q000187:drug effects; D004792:Enzyme Precursors / Q000378:metabolism; D006801:Humans; D006997:Hypochlorous Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D003012:Microbial Collagenase / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology*; D016877:Oxidants / Q000494:pharmacology*; D010664:Phenylmethylsulfonyl Fluoride / Q000494:pharmacology; D012697:Serine Endopeptidases; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004792:Enzyme Precursors; D016877:Oxidants; D010664:Phenylmethylsulfonyl Fluoride; D006997:Hypochlorous Acid; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; D017364:Collagenases; C022440:procollagenase; D003012:Microbial Collagenase; D013755:Tetradecanoylphorbol Acetate