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Blood, 15 May 2004, Vol. 103, No. 10, pp. 3837-3844. Prepublished online as a Blood First Edition Paper on January 15, 2004; DOI 10.1182/blood-2003-08-2806. This Article Full Text (PDF) All Versions of this Article: 2003-08-2806v1 103/10/3837    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 Tecchio, C. Articles by Cassatella, M. A Search for Related Content PubMed PubMed Citation Articles by Tecchio, C. Articles by Cassatella, M. A Social Bookmarking                   What's this? Submitted August 14, 2003 Accepted January 5, 2004 IFN-stimulated neutrophils and monocytes release a soluble form of TNF-related apoptosis-inducing ligand (TRAIL/Apo-2 ligand) displaying apoptotic activity on leukemic cells Cristina Tecchio, Veronica Huber, Patrizia Scapini, Federica Calzetti, Daniela Margotto, Giuseppe Todeschini, Lorenzo Pilla, Giovanni Martinelli, Giovanni Pizzolo, Licia Rivoltini, and Marco A Cassatella* Pathology, Section of General Pathology, University of Verona, Verona, Italy Unit of Immunotherapy of Human Tumors, Istituto Nazionale Tumori, Milano, Italy Department of Clinical and Experimental Medicine, University of Verona, Verona, Italy Institute of Hematology and Medical Oncology, University of Bologna, Bologna, Italy * Corresponding author; email: marco.cassatella{at}univr.it. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily exerting cytotoxic activities towards tumor cells. Herein, we demonstrate that therapeutic concentrations of IFN stimulate the expression of high levels of TRAIL mRNA and the release of elevated amounts of a soluble bioactive form of TRAIL (sTRAIL) in both human neutrophils and monocytes. Supernatants harvested from IFN-treated neutrophils/monocytes elicited, on TRAIL-sensitive leukemic cell lines, pro-apoptotic activities that were significantly reduced by either a combination of TRAIL-R1/Fc and TRAIL-R2/Fc chimeras or neutralizing anti-TRAIL, anti-TRAIL-R1 and anti-TRAIL-R2 antibodies, suggesting that they were mediated by released sTRAIL acting on both TRAIL receptors. Since diseases such as chronic myeloid leukemia (CML) and melanoma are effectively treated with IFN, we also demonstrate that CML neutrophils and PBMC cultured with IFN at therapeutic concentrations retain the capacity of releasing sTRAIL, suggesting that CML leukocytes, in vivo, might represent an important source of sTRAIL. In this regard, we show that sTRAIL serum levels as well as leukocyte-associated TRAIL significantly increase in melanoma patients following IFN administration. Collectively, these findings indicate that sTRAIL released by IFN-activated neutrophils and monocytes contributes not only to the immunoregulatory actions but also to the therapeutic activities of IFN. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Luce, A. Courtin, C. Levalois, S. Altmeyer-Morel, P.-H. Romeo, S. Chevillard, and J. Lebeau Death receptor pathways mediate targeted and non-targeted effects of ionizing radiations in breast cancer cells Carcinogenesis, March 1, 2009; 30(3): 432 - 439. [Abstract] [Full Text] [PDF] M. G. Brown, Y. Y. Huang, J. S. Marshall, C. A. King, D. W. Hoskin, and R. Anderson Dramatic caspase-dependent apoptosis in antibody-enhanced dengue virus infection of human mast cells J. Leukoc. 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