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Blood, 15 July 2004, Vol. 104, No. 2, pp. 586-593. Prepublished online as a Blood First Edition Paper on April 6, 2004; DOI 10.1182/blood-2003-12-4259. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-12-4259v1 104/2/586    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 Hildebrandt, G. C. Articles by Cooke, K. R. Search for Related Content PubMed PubMed Citation Articles by Hildebrandt, G. C. Articles by Cooke, K. R. Related Collections Immunobiology Transplantation Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Donor-derived TNF- regulates pulmonary chemokine expression and the development of idiopathic pneumonia syndrome after allogeneic bone marrow transplantation Gerhard C. Hildebrandt, Krystyna M. Olkiewicz, Leigh A. Corrion, Yayi Chang, Shawn G. Clouthier, Chen Liu, and Kenneth R. Cooke From the Departments of Pediatrics and Internal Medicine, Division of Hematology and Oncology, Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor; Department of Pathology, University of Michigan, Ann Arbor; and Department of Pathology, University of Florida School of Medicine, Gainesville. Idiopathic pneumonia syndrome (IPS) is a significant cause of mortality after allogeneic bone marrow transplantation (allo-BMT), and tumor necrosis factor- (TNF-) is a significant effector molecule in this process. However, the relative contribution of donor-versus host-derived TNF- to the development of IPS has not been elucidated. Using a lethally irradiated parent F1 mouse IPS model, we showed that 5 weeks after transplantation allo-BMT recipients developed significant lung injury compared with syngeneic controls, which was associated with increased bronchoalveolar lavage (BAL) fluid levels of TNF-, elevated numbers of donor-derived TNF--secreting T cells, and increased pulmonary macrophage production of TNF- to lipopolysaccharide (LPS) stimulation. Allo-BMT with TNF--/- donor cells resulted in significantly reduced IPS severity, whereas utilization of TNF--deficient mice as BMT recipients had no effect on IPS. We next determined that TNF- secretion from both donor accessory cells (monocytes/macrophages) and T cells significantly contributed to the development of IPS. Importantly, the absence of donor T-cell-derived TNF- resulted in a significant decrease in inflammatory chemokine production in the lung and near complete abrogation of IPS. Collectively, these data demonstrate that donor TNF- is critical to the development of IPS and reveal a heretofore unknown mechanism for T-cell-derived TNF- in the evolution of this process. (Blood. 2004;104:586-593) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. M. Marriott, P. G. Hellewell, S. S. Cross, P. G. Ince, M. K. B. Whyte, and D. H. Dockrell Decreased Alveolar Macrophage Apoptosis Is Associated with Increased Pulmonary Inflammation in a Murine Model of Pneumococcal Pneumonia J. Immunol., November 1, 2006; 177(9): 6480 - 6488. [Abstract] [Full Text] [PDF] C. A. Wysocki, A. Panoskaltsis-Mortari, B. R. Blazar, and J. S. Serody Leukocyte migration and graft-versus-host disease Blood, June 1, 2005; 105(11): 4191 - 4199. [Abstract] [Full Text] [PDF] M. Shukla, S. Yang, C. Milla, A. Panoskaltsis-Mortari, B. R. Blazar, and I. Y. Haddad Absence of host tumor necrosis factor receptor 1 attenuates manifestations of idiopathic pneumonia syndrome Am J Physiol Lung Cell Mol Physiol, May 1, 2005; 288(5): L942 - L949. [Abstract] [Full Text] [PDF] G. C. Hildebrandt, K. M. Olkiewicz, S. Choi, L. A. Corrion, S. G. Clouthier, C. Liu, J. S. Serody, and K. R. Cooke Donor T-cell production of RANTES significantly contributes to the development of idiopathic pneumonia syndrome after allogeneic stem cell transplantation Blood, March 15, 2005; 105(6): 2249 - 2257. [Abstract] [Full Text] [PDF]

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