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Blood, 29 January 2009, Vol. 113, No. 5, pp. 1112-1121. Prepublished online as a Blood First Edition Paper on September 18, 2008; DOI 10.1182/blood-2008-06-163832. This Article Full Text (PDF) Supplemental Figure and Videos All Versions of this Article: blood-2008-06-163832v1 113/5/1112    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 Flaumenhaft, R. Articles by Italiano, J. E. Search for Related Content PubMed PubMed Citation Articles by Flaumenhaft, R. Articles by Italiano, J. E., Jr. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 19, 2008 Accepted August 25, 2008 Megakaryocyte-derived microparticles: Direct visualization and distinction from platelet-derived microparticles Robert Flaumenhaft*, James R. Dilks, Jennifer Richardson, Eva Alden, Sunita R. Patel-Hett, Elisabeth Battinelli, Giannoula L. Klement, Martha Sola-Visner, and Joseph E. Italiano Jr. Division of Hemostasis and Thrombosis, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, United States Division of Hematology, Brigham and Women's Hospital, Boston, MA, United States Department of Vascular Biology, Children's Hospital Boston, Boston, MA, United States Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, United States Division of Newborn Medicine, Children's Hospital Boston, Boston, MA, United States * Corresponding author; email: rflaumen{at}bidmc.harvard.edu. Platelet microparticles are a normal constituent of circulating blood. Several studies have demonstrated positive correlations between thrombotic states and platelet microparticle levels. Yet little is known about the processes by which platelet microparticles are generated in vivo. We now characterize microparticles derived directly from megakaryocytes. Video microscopy of live mouse megakaryocytes demonstrated that microparticles form as submicron beads along the lengths of slender, unbranched micropodia. These microparticles are CD41+, CD42b+, and express surface phosphatidylserine. Megakaryocyte microparticle generation is resistant to inhibition of microtubule assembly, which is critical to platelet formation, and augmented by inhibition of actin polymerization. To determine whether circulating microparticles are derived primarily from activated platelets or megakaryocytes, we identified markers that distinguish between these two populations. CD62P and LAMP-1 were found only on mouse microparticles from activated platelets. In contrast, full-length filamin A was found in megakaryocyte-derived microparticles, but not microparticles from activated platelets. Circulating microparticles isolated from mice were CD62P-, LAMP-1- and expressed full-length filamin A indicating a megakaryocytic origin. Similarly, circulating microparticles isolated from healthy volunteers were CD62P- and expressed full-length filamin A. Cultured human megakaryocytes elaborated microparticles that were CD41+, CD42b+, and express surface phosphatidylserine. These results indicate that direct production by megakaryocytes represents a physiologic means to generate circulating platelet microparticles. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Megakaryocyte-derived microvesicles, please stand up! Mariusz Z. Ratajczak Blood 2009 113: 981-982. [Full Text] [PDF] This article has been cited by other articles: M. Prokopi, G. Pula, U. Mayr, C. Devue, J. Gallagher, Q. Xiao, C. M. Boulanger, N. Westwood, C. Urbich, J. Willeit, et al. Proteomic analysis reveals presence of platelet microparticles in endothelial progenitor cell cultures Blood, July 16, 2009; 114(3): 723 - 732. [Abstract] [Full Text] [PDF]

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