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Blood, 15 January 2005, Vol. 105, No. 2, pp. 464-473. Prepublished online as a Blood First Edition Paper on September 28, 2004; DOI 10.1182/blood-2003-12-4415. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-12-4415v1 105/2/464    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Emadi, S. Articles by Le Bousse-Kerdilès, M.-C. Search for Related Content PubMed PubMed Citation Articles by Emadi, S. Articles by Le Bousse-Kerdilès, M.-C. Related Collections Hematopoiesis and Stem Cells Hemostasis, Thrombosis, and Vascular Biology Neoplasia Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CHEMOKINES IL-8 and its CXCR1 and CXCR2 receptors participate in the control of megakaryocytic proliferation, differentiation, and ploidy in myeloid metaplasia with myelofibrosis Sharareh Emadi, Denis Clay, Christophe Desterke, Bernadette Guerton, Eliane Maquarre, Agnès Charpentier, Claude Jasmin, and Marie-Caroline Le Bousse-Kerdilès, for the French INSERM Research Network on MMM From the Institut National de la Santé et de la Recherche Médicale (INSERM), Unit 602, André Lwoff Institute, Paul Brousse Hospital, Villejuif, France; Department of Chemical and Material Engineering (CME), Arizona State University, Tempe AZ; and the Laboratory of Hematology, Saint-Vincent Hospital, Groupe Hospitalier de l'Institut Catholique de Lille, Lille Cedex, France. Myeloproliferation, myelofibrosis, and neoangiogenesis are the 3 major intrinsic pathophysiologic features of myeloid metaplasia with myelofibrosis (MMM). The myeloproliferation is characterized by an increased number of circulating CD34+ progenitors with the prominent amplification of dystrophic megakaryocytic (MK) cells and myeloid metaplasia in the spleen and liver. The various biologic activities of interleukin 8 (IL-8) in hematopoietic progenitor proliferation and mobilization as well as in neoangiogenesis prompted us to analyze its potential role in MMM. We showed that the level of IL-8 chemokine is significantly increased in the serum of patients and that various hematopoietic cells, including platelets, participate in its production. In vitro inhibition of autocrine IL-8 expressed by CD34+ cells with either a neutralizing or an antisense anti–IL-8 treatment increases the proliferation of MMM CD34+-derived cells and stimulates their MK differentiation. Moreover, addition of neutralizing anti–IL-8 receptor (CXC chemokine receptor 1 [CXCR1] or 2 [CXCR2]) antibodies to MMM CD34+ cells cultured under MK liquid culture conditions increases the proliferation and differentiation of MMM CD41+ MK cells and restores their polyploidization. Our results suggest that IL-8 and its receptors participate in the altered MK growth that features MMM and open new therapeutic prospects for this still incurable disease. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J.-J. Lataillade, O. Pierre-Louis, H. C. Hasselbalch, G. Uzan, C. Jasmin, M.-C. Martyre, M.-C. Le Bousse-Kerdiles, and on behalf of the French INSERM and the European EU Does primary myelofibrosis involve a defective stem cell niche? From concept to evidence Blood, October 15, 2008; 112(8): 3026 - 3035. [Abstract] [Full Text] [PDF] L. Zheng, C.-n. Njauw, and M. Martins-Green A hCXCR1 transgenic mouse model containing a conditional color-switching system for imaging of hCXCL8/IL-8 functions in vivo J. Leukoc. Biol., November 1, 2007; 82(5): 1247 - 1256. [Abstract] [Full Text] [PDF] Z. B. Levashova, N. Sharma, O. A. Timofeeva, J. S. Dome, and A. O. Perantoni ELR+-CXC Chemokines and Their Receptors in Early Metanephric Development J. Am. Soc. Nephrol., August 1, 2007; 18(8): 2359 - 2370. [Abstract] [Full Text] [PDF] J. A. Coppinger, R. O'Connor, K. Wynne, M. Flanagan, M. Sullivan, P. B. Maguire, D. J. Fitzgerald, and G. Cagney Moderation of the platelet releasate response by aspirin Blood, June 1, 2007; 109(11): 4786 - 4792. [Abstract] [Full Text] [PDF] Z. Chen, M. Hu, and R. A. Shivdasani Expression analysis of primary mouse megakaryocyte differentiation and its application in identifying stage-specific molecular markers and a novel transcriptional target of NF-E2 Blood, February 15, 2007; 109(4): 1451 - 1459. [Abstract] [Full Text] [PDF]

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