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Blood, 1 November 2006, Vol. 108, No. 9, pp. 3012-3020. Prepublished online as a Blood First Edition Paper on June 20, 2006June 15, 2006; DOI 10.1182/blood-2006-04-019109. This Article Full Text (PDF) All Versions of this Article: blood-2006-04-019109v1 blood-2006-04-019109v2 108/9/3012    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 Martinez, M. C Articles by Freyssinet, J.-M. Search for Related Content PubMed PubMed Citation Articles by Martinez, M. C Articles by Freyssinet, J.-M. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 24, 2006 Accepted May 22, 2006 Transfer of differentiation signal by membrane microvesicles harboring hedgehog morphogens Maria C Martinez, Frederic Larbret, Fatiha Zobairi, Josee Coulombe, Najet Debili, William Vainchenker, Martial Ruat, and Jean-Marie Freyssinet* INSERM, Unite 770, Strasbourg, France INSERM, Unite 790, Institut Gustave Roussy, Villejuif, France CNRS UPR 9040, IFR 2118, Laboratoire de Neurobiologie Cellulaire et Moleculaire, France U790 Inserm, Institut Gustave Roussy * Corresponding author; email: jean-marie.freyssinet{at}hemato-ulp.u-strasbg.fr. Hedgehog (Hh) proteins are considered diffusible morphogens that can be membrane anchored, playing an essential role during development. Here we show that Hh morphogens are associated to microvesicles shed from the plasma membrane of apoptotic/stimulated T cells. Hh+ microvesicles induced differentiation of human K562 pluripotent erythroleukemic cells towards megakaryocytic lineage, as testified to by the expression of IIb3 integrin and CD42b and changes in the cell cycle. Blocking Hh pathway with either cyclopamine, neutralizing antibodies or inhibitors of the protein kinase A pathway resulted in the inhibition of these effects. Activation of Hh signaling by SAG, a synthetic agonist, mimicked Hh+ microvesicles effects on K562 cells. Human Hh+ microvesicles, circulating in vivo or derived from apoptotic/stimulated lymphocytes from healthy and diabetic individuals, elicited K562 cell differentiation, also inhibited by cyclopamine. In addition, Hh+ microvesicles-treated primary human CD34+ cells presented an increase of CD41+CD42- and CD41+CD42+ megakaryocytic populations with an increase of corresponding polyploidy, both being reduced by blockers of the Hh pathway. Because virtually all cell types undergo plasma membrane remodelling when stimulated, derived microvesicles can therefore be considered true vectors in the transfer of morphogen-borne biological information to remote responsive cells, and thereby contribute to the maintenance of homeostasis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Microvesicles: from "dust to crown" Mariusz Z. Ratajczak Blood 2006 108: 2885-2886. [Full Text] [PDF] This article has been cited by other articles: F. Angelot, E. Seilles, S. Biichle, Y. Berda, B. Gaugler, J. Plumas, L. Chaperot, F. Dignat-George, P. Tiberghien, P. Saas, et al. Endothelial cell-derived microparticles induce plasmacytoid dendritic cell maturation: potential implications in inflammatory diseases Haematologica, November 1, 2009; 94(11): 1502 - 1512. [Abstract] [Full Text] [PDF] R. Soleti, T. Benameur, C. Porro, M. A. Panaro, R. Andriantsitohaina, and M. C. Martinez Microparticles harboring Sonic Hedgehog promote angiogenesis through the upregulation of adhesion proteins and proangiogenic factors Carcinogenesis, April 1, 2009; 30(4): 580 - 588. [Abstract] [Full Text] [PDF] D. Castellana, F. Zobairi, M. C. Martinez, M. A. Panaro, V. Mitolo, J.-M. Freyssinet, and C. Kunzelmann Membrane Microvesicles as Actors in the Establishment of a Favorable Prostatic Tumoral Niche: A Role for Activated Fibroblasts and CX3CL1-CX3CR1 Axis Cancer Res., February 1, 2009; 69(3): 785 - 793. [Abstract] [Full Text] [PDF] H. A. Mostefai, F. Meziani, M. L. Mastronardi, A. Agouni, C. Heymes, C. Sargentini, P. Asfar, M. C. Martinez, and R. Andriantsitohaina Circulating Microparticles from Patients with Septic Shock Exert Protective Role in Vascular Function Am. J. Respir. Crit. Care Med., December 1, 2008; 178(11): 1148 - 1155. [Abstract] [Full Text] [PDF] H. A. Mostefai, A. Agouni, N. Carusio, M. L. Mastronardi, C. Heymes, D. Henrion, R. Andriantsitohaina, and M. C. Martinez Phosphatidylinositol 3-Kinase and Xanthine Oxidase Regulate Nitric Oxide and Reactive Oxygen Species Productions by Apoptotic Lymphocyte Microparticles in Endothelial Cells J. Immunol., April 1, 2008; 180(7): 5028 - 5035. [Abstract] [Full Text] [PDF] A. Agouni, H. A. Mostefai, C. Porro, N. Carusio, J. Favre, V. Richard, D. Henrion, M. C. Martinez, and R. Andriantsitohaina Sonic hedgehog carried by microparticles corrects endothelial injury through nitric oxide release FASEB J, September 1, 2007; 21(11): 2735 - 2741. [Abstract] [Full Text] [PDF]

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