title: Localization and translocation of MMP-2 during aggregation of human platelets.
abstract: We have previously shown that human platelets express matrix metalloproteinase-2 (MMP-2) and that the release of this enzyme during platelet activation mediates the ADP- and thromboxane-independent part of aggregation. We have now used immunogold electron microscopy, flow cytometry. Western blot analysis and zymography methods to study the ultrastructural localization of MMP-2 in human washed platelets. Platelet aggregation was stimulated by collagen and the MMP-2 immunoreactivity of platelets was followed during various stages of aggregation. In resting platelets, MMP-2 was randomly distributed in the platelet cytosol without detectable association with platelet granules. Platelet aggregation caused the translocation of MMP-2 from the cytosol to the extracellular 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.
authors.affiliation: Department of Pharmacology, University of Alberta, Edmonton, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Sawicki
authors.forename: E J
authors.initials: EJ
authors.lastname: Sanders
authors.forename: E
authors.initials: E
authors.lastname: Salas
authors.forename: M
authors.initials: M
authors.lastname: Wozniak
authors.forename: J
authors.initials: J
authors.lastname: Rodrigo
authors.forename: M W
authors.initials: MW
authors.lastname: Radomski
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D001692:Biological Transport; D001792:Blood Platelets / Q000201:enzymology* / Q000648:ultrastructure; D002462:Cell Membrane / Q000201:enzymology; D003094:Collagen / Q000494:pharmacology; D003600:Cytosol / Q000201:enzymology; D005110:Extracellular Space / Q000201:enzymology; D005434:Flow Cytometry; D018093:Gelatinases / Q000097:blood*; D006801:Humans; D007150:Immunohistochemistry; D020778:Matrix Metalloproteinase 2; D008666:Metalloendopeptidases / Q000097:blood*; D010974:Platelet Aggregation / Q000187:drug effects
chemical_list: D000244:Adenosine Diphosphate; D003094:Collagen; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2