Human platelet collagenase.
The presence of proteolytic enzymes such as cathepsin and elastase in platelets and the important role of collagen in platelet aggregation suggested that collagenase might be present in platelets. Epinephrine, ADP, and collagen liberate collagenase from platelets in plasma as measured by the hydrolysis of [(14)C]glycine-labeled collagen fibrils. The collagenase activity appeared in an early phase of platelet aggregation and was not a part of the release reaction. However, only 50% of the total collagenase could be liberated by the aggregating agents used. Sucrose density gradient analysis of platelet homogenates using appropriate sub-cellular markers indicated that collagenase appeared in both the granule and membrane fractions. Gel-filtered platelets failed to show collagenase activity before exposure to aggregating agents but released more collagenolytic activity than was found in platelet-rich plasma. This observation was explained by the finding that collagenolytic activity was inhibited by normal human plasma. One of the inhibitors is alpha(1)-antitrypsin as demonstrated by decreased inhibition in plasma from a patient with homozygous alpha(1)-antitrypsin deficiency. Platelet collagenase activity could also be demonstrated by its ability to decrease the viscosity of collagen solutions and to produce collagen fragments similar to those produced by other mammalian collagenases on disk gel electrophoresis. The observation that partially purified platelet collagenase could destroy the platelet-aggregating activity of collagen suggests that the enzyme might function in a negative feedback mechanism limiting thrombus formation.
D000135:Acid Phosphatase / Q000097:blood; D000244:Adenosine Diphosphate / Q000097:blood; D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000201:enzymology* / Q000378:metabolism; D001798:Blood Proteins / Q000032:analysis; D001809:Blood Viscosity; D002021:Buffers; D002250:Carbon Radioisotopes; D002850:Chromatography, Gel; D003080:Cold Temperature; D003094:Collagen / Q000378:metabolism; D004492:Edetic Acid / Q000494:pharmacology; D004589:Electrophoresis, Disc; D004591:Electrophoresis, Polyacrylamide Gel; D005966:Glucuronidase / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D003012:Microbial Collagenase / Q000037:antagonists & inhibitors / Q000097:blood* / Q000302:isolation & purification / Q000378:metabolism; D009708:Nucleotidases / Q000097:blood; D010973:Platelet Adhesiveness / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism; D014461:Ultracentrifugation
D001798:Blood Proteins; D002021:Buffers; D002250:Carbon Radioisotopes; D012701:Serotonin; D000244:Adenosine Diphosphate; D003094:Collagen; D004492:Edetic Acid; D009708:Nucleotidases; D000135:Acid Phosphatase; D005966:Glucuronidase; D003012:Microbial Collagenase; D001241:Aspirin