Platelet-derived collagenase inhibitor: characterization and subcellular localization.
Purified human platelets were found to contain a collagenase inhibitor that is immunologically, functionally, and chromatographically identical to that produced by human skin fibroblasts. None of the other formed elements of the blood (erythrocytes, granulocytes, mononuclear cells) possessed detectable quantities of this protein. Virtually all the collagenase inhibitor contained within platelets was released following platelet activation with thrombin. Similarly, platelet activation accompanying blood clotting also resulted in the release of this protein, the ratio of plasma to serum inhibitor levels being approximately equal to 0.5. When platelets were subjected to subcellular fractionation, essentially all of the platelet-associated collagenase inhibitor was found to be located in the alpha-granule. Studies with radiolabeled inhibitor failed to detect uptake of inhibitor by platelets. Furthermore, immunologically reactive protein of similar quantity to that found in platelets was identified in human megakaryocyte lysates. Thus, the data suggest that the collagenase inhibitor is endogenously produced and stored within platelet alpha-granules. The platelet-derived collagenase inhibitor was antigenically identical to the collagenase inhibitor from human skin fibroblasts in double immunodiffusion and, like its fibroblast counterpart, inhibited collagenase on a 1:1 stoichiometric basis. When subjected to several of the chromatographic procedures utilized to purify the fibroblast protein, the platelet inhibitor behaved in an indistinguishable manner. Platelet factor 4, previously reported to be a collagenase inhibitor, was found to be immunologically unrelated to the platelet-derived collagenase inhibitor. Furthermore, platelet factor 4 displayed no collagenase inhibitory activity. Although the function of platelet-derived collagenase inhibitor is unknown, such a protein released by activated platelets may serve to regulate collagen turnover during the early stages of the inflammatory process.
Cooper
T W
TW
Eisen
A Z
AZ
Stricklin
G P
GP
Welgus
H G
HG
D001792:Blood Platelets / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000097:blood* / Q000276:immunology / Q000302:isolation & purification; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D003012:Microbial Collagenase / Q000037:antagonists & inhibitors*; D010978:Platelet Factor 4 / Q000302:isolation & purification; D012867:Skin / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases
D004791:Enzyme Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases; D010978:Platelet Factor 4; D003012:Microbial Collagenase