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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 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 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 Giron-Michel, J. Articles by Azzarone, B. Search for Related Content PubMed PubMed Citation Articles by Giron-Michel, J. Articles by Azzarone, B. Related Collections Hematopoiesis and Stem Cells Cell Adhesion and Motility Signal Transduction Gene Expression Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 July 2003, Vol. 102, No. 1, pp. 109-117 HEMATOPOIESIS Differential STAT3, STAT5, and NF-B activation in human hematopoietic progenitors by endogenous interleukin-15: implications in the expression of functional molecules Julien Giron-Michel, Anne Caignard, Manuela Fogli, Danièle Brouty-Boyé, Diane Briard, Marc van Dijk, Raffaella Meazza, Silvano Ferrini, Caroline Lebousse-Kerdilès, Denis Clay, Heidi Bompais, Salem Chouaib, Bruno Péault, and Bruno Azzarone From U 506 Institut National Santé et Recherche Medicale (INSERM), U 542 INSERM, and U 268 INSERM, Hôpital Paul Brousse, Villejuif; U 487 INSERM, IGR, Villejuif, France; Istituto Gaslini, Genoa; Isitituto Nazionale per la Ricerca sul Cancro IST, Genoa, Italy; and Genmab, Utrecht, the Netherlands. Different forms of interleukin-15 (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, nuclear factor- B (NF- B) was activated in bone marrow (BM) and cord blood (CB) progenitors, whereas signal transducer and activator of transcription 3 (STAT3) and STAT5 activation was restricted to peripheral granulocyte—colony-stimulating factor (G-CSF)—mobilized and BM progenitors, respectively. ES-IL-15 acts through autocrine/paracrine loops controlled by high-affinity receptors involving IL-15 receptor (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 monoclonal antibody (mAb) inhibits the expression of the c chain and of the chemokine stromal derived factor-1 (SDF-1) but had no effect on vascular cell adhesion molecule 1 (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 important, up-regulated SDF-1 expression. In conclusion, unprimed human hematopoietic CD34+ cells secrete cell-unbound IL-15, which activates through autocrine/paracrine loop distinct signaling pathways, depending on the progenitor source, thereby influencing the expression of several molecules important in the control of hematopoiesis. 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