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Prepublished online as a Blood First Edition Paper on August 7, 2003; DOI 10.1182/blood-2003-04-1305. This Article Full Text (PDF) All Versions of this Article: 2003-04-1305v1 102/12/4229    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Bergmeier, W. Articles by Wagner, D. D Search for Related Content PubMed PubMed Citation Articles by Bergmeier, W. Articles by Wagner, D. D Social Bookmarking                   What's this? Submitted April 25, 2003 Accepted July 27, 2003 Metalloproteinase inhibitors improve the recovery and hemostatic function of in vitro aged or injured mouse platelets Wolfgang Bergmeier, Peter C Burger, Crystal L Piffath, Karin M Hoffmeister, John H Hartwig, Bernhard Nieswandt, and Denisa D Wagner* The Center for Blood Research, Boston, MA, USA; Department of Pathology, Harvard Medical School, Boston, MA, USA Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA Rudolf Virchow Center for Experimental Biomedicine, University of Wuerzburg, Wuerzburg, Germany * Corresponding author; email: wagner{at}cbr.med.harvard.edu. Platelet transfusions are a crucial component of support for patients with severe thrombocytopenia. Storage of platelet concentrates, however, is associated with a reduction in platelet posttransfusion recovery and hemostatic function. In this study, we established a model of mitochondrial injury that resembles platelet storage lesion. Mitochondrial injury, provoked by incubation of platelets with carbonyl cyanide m-chlorophenylhydrazone (CCCP), led to reduced posttransfusion recovery in mice, an effect that directly correlated with the duration of treatment. Damaged platelets were characterized by shape change, disruption of membrane asymmetry, surface expression of P-selectin, and profound proteolysis of GPIb. Using our model, we identified a key role for endogenous metalloproteinase(s) in platelet clearance, as their inhibition markedly improved posttransfusion recovery of both the mitochondria-injured and in vitro aged mouse platelets. Metalloproteinase inhibition also prevented proteolysis of GPIb on damaged platelets thereby improving the hemostatic function of these cells in vivo. We propose that inhibition of metalloproteinase activity during storage could significantly improve the effectiveness of platelet transfusions. Surface expression of GPIb might be a powerful marker to determine the quality of platelet concentrates as it reflects metalloproteinase activity in vitro. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Cheng, R. Yan, S. Li, Y. Yuan, J. Liu, C. Ruan, and K. Dai Shear-induced interaction of platelets with von Willebrand factor results in glycoprotein Ib{alpha} shedding Am J Physiol Heart Circ Physiol, December 1, 2009; 297(6): H2128 - H2135. [Abstract] [Full Text] [PDF] H. Falet, M. P. Marchetti, K. M. Hoffmeister, M. J. Massaad, R. S. Geha, and J. H. Hartwig Platelet-associated IgAs and impaired GPVI responses in platelets lacking WIP Blood, November 19, 2009; 114(21): 4729 - 4737. [Abstract] [Full Text] [PDF] H. Nishikii, K. Eto, N. Tamura, K. Hattori, B. 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