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Prepublished online as a Blood First Edition Paper on October 24, 2002; DOI 10.1182/blood-2002-07-2184. This Article Full Text (PDF) All Versions of this Article: 2002-07-2184v1 101/4/1316    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 Casella, I. Articles by Peschle, C. Search for Related Content PubMed PubMed Citation Articles by Casella, I. Articles by Peschle, C. Social Bookmarking                   What's this? Submitted July 22, 2002 Accepted September 12, 2002 Autocrine-paracrine VEGF loops potentiate the maturation of megakaryocytic precursors through Flt1 receptor Ida Casella, Tiziana Feccia, Cristiana Chelucci, Paola Samoggia, Germana Castelli, Raffaella Guerriero, Isabella Parolini, Eleonora Petrucci, Elvira Pelosi, Ornella Morsilli, Marco Gabbianelli, Ugo Testa, and Cesare Peschle* Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA, USA Department of Hematology-Oncology, Istituto Superiore di Sanita', Rome, Italy * Corresponding author; email: cesare.peschle{at}mail.tju.edu. The expression/function of VEGF receptors (VEGFR1/Flt1 and VEGFR2/KDR/Flk1) in hematopoiesis is under scrutiny. We have investigated the expression of Flt1 and KDR on hematopoietic precursors, as evaluated in liquid culture of CD34+ hematopoietic progenitor cells (HPCs) induced to unilineage differentiation/maturation through the erythroid (E), megakaryocytic (Mk), granulocytic (G) or monocytic (Mo) lineage. KDR, expressed on 0.5-1.5% CD34+ cells, is rapidly downmodulated upon induction of differentiation. Similarly, Flt1 is present at very low levels in HPCs and is downmodulated in E and G lineages; however, Flt1 is induced in the precursors of both Mo and Mk series, i.e., its level progressively increases during Mo maturation, while it peaks at the initial-intermediate culture stages in the Mk lineage. Functional experiments indicate that Mk and E, but not G and Mo precursors release significant amounts of VEGF in the culture medium, particularly at low O2 level. The functional role of VEGF release on Mk maturation is indicated by two series of observations. (a) Molecules preventing the VEGF-Flt1 interaction on the precursor membrane (e.g., soluble Flt1 receptors) significantly inhibit Mk polyploidization. (b) Addition of exogenous VEGF or PlGF markedly potentiates Mk maturation. Conversely, VEGF does not modify Mo differentiation/maturation. Altogether, our results suggest that in the hematopoietic microenvironment an autocrine VEGF loop contributes to optimal Mk maturation through Flt1. A paracrine loop involving VEGF release by E precursors may also operate. Similarly, recent studies indicate that an autocrine loop involving VEGF and Flt1/Flk1 receptors mediates hematopoietic stem cells survival and differentiation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y. Huang, X. Chen, M. M. Dikov, S. V. Novitskiy, C. A. Mosse, L. Yang, and D. P. 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