or: Characterization and

Purified human platelets were found to con- tain a collagenase inhibitor that is immunologically, function- ally, and chromatographically identical to that produced by human skin fibroblasts. None of the other formed elements of the blood (erythrocytes, granulocytes, mononuclear cells) pos- sessed 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 re- lease of this protein, the ratio of plasma to serum inhibitor levels being -0.5. When platelets were subjected to subcellu- lar fractionation, essentially all of the platelet-associated colla- genase inhibitor was found to be located in the a-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 identi- fied in human megakaryocyte lysates. Thus, the data suggest that the collagenase inhibitor is endogenously produced and stored within platelet a-granules. The platelet-derived collage- nase inhibitor was antigenically identical to the collagenase in- hibitor from human skin fibroblasts in double immunodiffu- sion 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 collage- nase inhibitor, was found to be immunologically unrelated to the platelet-derived collagenase inhibitor. Furthermore, plate- let factor 4 displayed no collagenase inhibitory activity. Al- though 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.