Cathepsin G degrades denatured collagen.
Neutrophils are known to contain several metalloproteinases that can damage collagen, a major structural component of the extracellular matrix. Here a neutrophil serine proteinase secreted from activated neutrophils was shown to cleave denatured collagen (gelatin). This serine proteinase was not inhibited by synthetic inhibitors of elastase (elastatinal or Me-O-suc-Ala-Pro-Val-CH2Cl). However, a synthetic inhibitor of cathepsin G (Z-Gly-Leu-Phe-CH2Cl) was able to inhibit the serine proteinase having gelatinolytic activity, indicating that cathepsin G, a major serine proteinase, from neutrophils is responsible for cleaving gelatin. Purified cathepsin G was also shown to degrade gelatin. In further experiments, oxidized glutathione was able to enhance the gelatinolytic activity of cathepsin G. These results show that cathepsin G is capable of cleaving denatured collagen, and its activity is enhanced or stabilized in the presence of glutathione. The data support the concept that cathepsin G released from neutrophils could play a major role in degrading collagen during inflammation and may in part account for the degradation of extracellular matrix during inflammation.
Capodici
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UMDNJ-Robert Wood Johnson Medical School, Department of Biochemistry, Piscataway 08854.
Berg
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D000818:Animals; D056649:Cathepsin G; D002403:Cathepsins / Q000494:pharmacology*; D002478:Cells, Cultured; D002642:Chick Embryo; D003094:Collagen / Q000378:metabolism*; D004492:Edetic Acid / Q000494:pharmacology; D005780:Gelatin / Q000378:metabolism; D006801:Humans; D009504:Neutrophils / Q000201:enzymology*; D010662:Phenylmercuric Acetate / Q000031:analogs & derivatives / Q000494:pharmacology; D010664:Phenylmethylsulfonyl Fluoride / Q000494:pharmacology; D012697:Serine Endopeptidases
D010664:Phenylmethylsulfonyl Fluoride; C010024:4-aminophenylmercuriacetate; D005780:Gelatin; D003094:Collagen; D004492:Edetic Acid; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; D010662:Phenylmercuric Acetate