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Blood, 15 March 2004, Vol. 103, No. 6, pp. 2417-2426. Prepublished online as a Blood First Edition Paper on November 13, 2003; DOI 10.1182/blood-2003-08-2708. This Article Full Text (PDF) All Versions of this Article: 2003-08-2708v1 103/6/2417    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 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 Social Bookmarking                   What's this? Submitted August 11, 2003 Accepted November 1, 2003 A critical role for CCR2/MCP-1 interactions in the development of idiopathic pneumonia syndrome after allogeneic bone marrow transplantation Gerhard C Hildebrandt, Ulrich A Duffner, Krystyna M Olkiewicz, Leigh A Corrion, Nicole E Willmarth, Debra L Williams, Shawn G Clouthier, Cory M Hogaboam, Pavan R Reddy, Bethany B Moore, Chen Liu, Gregory Yanik, and Kenneth R Cooke* Department of Pediatrics, Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor, MI, USA; Department of Internal Medicine, Division of Hematology and Oncology, Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor, MI, USA Department of Internal Medicine, Division of Pulmonology and Critical Care, University of Michigan, Ann Arbor, MI, USA Department of Pathology, University of Michigan, Ann Arbor, MI, USA Department of Pathology, University of Florida School of Medicine, Gainesville, FL, USA * Corresponding author; email: krcooke{at}umich.edu. Idiopathic pneumonia syndrome (IPS) is a major complication after allogeneic (allo-) bone marrow transplantation (BMT) and involves the infiltration of donor leukocytes and the secretion of inflammatory cytokines. We hypothesized that leukocyte recruitment during IPS is dependent in part upon interactions between CCR2 and its primary ligand monocyte chemoattractant protein-1 (MCP-1). To test this hypothesis, IPS was induced in a lethally irradiated parentF1 mouse BMT model. Compared to syngeneic controls, pulmonary expression of MCP-1 and CCR2 mRNA was significantly increased after allo-BMT. Transplantation of CCR2 deficient (CCR2-/-) donor cells resulted in a significant reduction in IPS severity compared to BMT with wild type (CCR2+/+) cells and in reduced BAL fluid cellularity and BAL levels of TNF and sTNFR I. In addition, neutralization of MCP-1 resulted in significantly decreased lung injury compared to control treated allogeneic recipients. Experimental data correlated with preliminary clinical findings; patients with IPS have elevated levels of MCP-1 in the BAL fluid at the time of diagnosis. Collectively, these data demonstrate that CCR2/MCP-1 interactions significantly contribute to the development of experimental IPS and suggest that interventions blocking these receptor:ligand interactions may represent novel strategies to prevent or treat this lethal complication after allo-BMT. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. R. Engel, J. Maurer, A. P. Tittel, C. Weisheit, T. Cavlar, B. Schumak, A. Limmer, N. van Rooijen, C. Trautwein, F. Tacke, et al. CCR2 Mediates Homeostatic and Inflammatory Release of Gr1high Monocytes from the Bone Marrow, but Is Dispensable for Bladder Infiltration in Bacterial Urinary Tract Infection J. Immunol., October 15, 2008; 181(8): 5579 - 5586. [Abstract] [Full Text] [PDF] G. A. Yanik, V. T. Ho, J. 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