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Prepublished online as a Blood First Edition Paper on March 6, 2003; DOI 10.1182/blood-2002-09-2760. This Article Full Text (PDF) All Versions of this Article: 2002-09-2760v1 102/1/109    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 Giron-Michel, J. Articles by Azzarone, B. Search for Related Content PubMed PubMed Citation Articles by Giron-Michel, J. Articles by Azzarone, B. Social Bookmarking                   What's this? Submitted September 10, 2002 Accepted February 23, 2003 Differential STAT3, STAT5, and NF-B activation in human hematopoietic progenitors by an endogenous interleukin-15: implications in the expression of functional molecules Julien Giron-Michel, Anne Caignard, Manuela Fogli, Daniele Brouty-Boye, Diane Briard, Marc van Dijk, Raffaella Meazza, Silvano Ferrini, Caroline Lebousse-Kerdiles, Denis Clay, Heidi Bompais, Salem Chouaib, Bruno Peault, and Bruno Azzarone* Department of Hematology, Unite 506 INSERM, Villejuif, France Department of Immunology, IST, Genova, Italy Department of Hematology, Unite 268 INSERM, Villejuif, France Genmab, Utrecht, The Netherlands Department of Hematology, Unite 487 INSERM IGR, Villejuif, France Department of Hematology, Unite 542 INSERM, Villejuif, France Department of Immunology, Istituto Gaslini, Genova, Italy * Corresponding author; email: bazzarone{at}hotmail.com. Different forms of IL-15 have been identified and shown to elicit different transduction pathways whose impact on hematopoiesis is poorly understood. We demonstrated herein that hematopoietic CD34+ cells constitutively produced endogenous secreted-IL-15 (ES-IL-15) that activated different transcription factors and controlled the expression of several functional proteins depending on the progenitor source. Thus, NF-B was activated in bone marrow (BM) and cord blood (CB) progenitors whereas STAT3 and STAT5 activation was restricted to peripheral G-CSF-mobilized and BM progenitors, respectively. ES-IL-15 acts trough autocrine/paracrine loops controlled by high affinity receptors involving the IL-15R. Furthermore, ES-IL-15 was found to differentially control the expression of several functional molecules important for hematopoietic differentiation. Indeed, in BM precursors neutralizing anti-IL-15 mAb inhibit the expression of the c chain and of the chemokine SDF-1 but had no effect on the VCAM-1 and 1 integrin adhesion molecule expression. Conversely, in CB progenitors, anti-IL-15 mAb inhibited VCAM-1 and 1 integrin expression without affecting c chain expression and, most importantly, up-regulated SDF-1 expression. In conclusion, unprimed human hematopoietic CD34+ cells secrete a cell-unbound IL-15, which activates trough autocrine/paracrine loops distinct signaling pathway depending on the progenitor source, thereby influencing the expression of several molecules important in the control of hematopoiesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Fontalba, O. Gutierrez, and J. L. Fernandez-Luna NLRP2, an Inhibitor of the NF-{kappa}B Pathway, Is Transcriptionally Activated by NF-{kappa}B and Exhibits a Nonfunctional Allelic Variant J. 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