Activation of latent collagenase from polymorphonuclear leukocytes by oxygen radicals.
Polymorphonuclear leukocytes (PMN) accumulating at inflammatory sites have the potential to degrade collagen by releasing the metalloproteinase collagenase (EC 3.4.24.7), which is stored within the specific granules of these cells in a latent, inactive, form. In order to elucidate the activation mechanism the latent enzyme (molecular weight 91,000) was purified from human PMN and incubated with the oxygen radical-generating system of xanthine oxidase (EC 1.1.3.22) and hypoxanthine. This coincubation resulted in the activation of the latent enzyme as assessed by the collagenolytic attack on human and bovine cartilaginous tissue. Two parameters for collagenolysis were used: loss of hydroxyproline-containing fragments, and mechanical measurements reflecting the stability of tissue specimens. Superoxide dismutase (EC 1.15.1.1) as well as catalase (EC 1.11.1.6) were capable of inhibiting the activation of latent PMN collagenase by the oxygen radical-generating system. The results indicate the hydroxyl radical to be the final oxidant responsible for the activation of latent PMN collagenase. Thus a new activation mechanism of latent collagenase is presented in this paper and discussed together with the potential relevance in pathophysiologic states of acute and chronic inflammation.
D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism; D002417:Cattle; D004789:Enzyme Activation; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000378:metabolism; D003012:Microbial Collagenase / Q000097:blood*; D009504:Neutrophils / Q000201:enzymology*; D010100:Oxygen / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism
D007042:Hypoxanthines; D013481:Superoxides; D019271:Hypoxanthine; D006861:Hydrogen Peroxide; D014969:Xanthine Oxidase; D003012:Microbial Collagenase; D010100:Oxygen