Hypochlorous acid (HOCl) activation of neutrophil collagenase requires cathepsin G.
In an effort to understand the mechanism of collagenase activation in inflammation, human peripheral neutrophils were isolated and incubated with the tumor promoter, phorbol myristate acetate (PMA), which induces the neutrophils to degranulate and secrete proteinases. Neutrophil media were then treated with HOCl with or without various proteinase inhibitors then collagenase activity was measured. Added HOCl was able to activate latent collagenase. However, a serine proteinase, cathepsin G, was found to be necessary for collagenase activation to occur by HOCl. The results indicate that cathepsin G is a key mediator in neutrophil collagenase activation and that HOCl under certain conditions leads to the activation of cathepsin G or the stimulation of cathepsin G's ability to activate neutrophil collagenase.
Capodici
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UMDNJ-Robert Wood Johnson Medical School, Department of Biochemistry, Piscataway, NJ 08854.
Berg
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D000818:Animals; D056649:Cathepsin G; D002403:Cathepsins / Q000494:pharmacology*; D002642:Chick Embryo; D003094:Collagen / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005978:Glutathione / 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*; D012697:Serine Endopeptidases
D006997:Hypochlorous Acid; D003094:Collagen; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; D003012:Microbial Collagenase; D005978:Glutathione