LOCALIZATION AND TRANSLOCATION OF MMP-2 DURING AGGREGATION OF HUMAN PLATELETS

We have previously shown that human platelets express matrix metallopr oteinase-2 (MMP-2) and that the release of this enzyme during platelet activation mediates the ADP- and thromboxane-independent part of aggr egation. We have now used immunogold electron microscopy, flow cytomet ry, Western blot analysis and zymography methods to study the ultrastr uctural localization of MMP-2 in human washed platelets. Platelet aggr egation was stimulated by collagen and the MMP-2 immunoreactivity of p latelets was followed during various stages of aggregation. In resting platelets, MMP-2 was randomly distributed in the platelet cytosol wit hout detectable association with platelet granules. Platelet aggregati on caused the translocation of MMP-2 from the cytosol to the extracell ular space. During the early stages of aggregation, MMP-2 remained in close association with the platelet plasma membrane. We conclude that the interactions of MMP-2 with platelet surface membranes mediate the aggregatory response induced by this enzyme.