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Elevated Levels of Monocyte Chemoattractant Protein-1 Are Associated With Bronchiolitis Obliterans Syndrome, a Fibrotic Disease of the Small Airways*

John A. Belperio, MD; M. P. Keane, MBBCh, FCCP; M. D. Burdick, MBBCh, FCCP; J. P. Lynch, III, MD, FCCP; Y. Y. Xue; S. L. Kuntel, MD; R. M. Strieter, MD
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*From the University of Michigan Medical School (Drs. Belperio, Keane, Lynch, Xue, and Kuntel), Ann Arbor, MI; and the UCLA School of Medicine (Drs. Burdick and Strieter), Los Angeles, CA.

Correspondence to: John A. Belperio, MD, Department of Internal Medicine, University of Michigan Health System, 1150 W Medical Center Dr, 6301 MSRB 111, Ann Arbor, MI 48109-0641



Chest. 2001;120(1_suppl):S2. doi:10.1378/chest.120.1_suppl.S2
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(CHEST 2001; 120:2S)

The major limitation to survival after lung transplantation is bronchiolitis obliterans syndrome (BOS), which is characterized by peribronchiolar leukocyte infiltration, deposition of extracellular matrix, and fibro-obliteration of the airways. BOS appears to be a chronic immunologic process resulting in an overexuberant reparative process. Critical to wound repair are activated mononuclear phagocytes. The CC chemokine, monocyte chemoattractant protein (MCP)-1, is a potent mononuclear phagocyte chemoattractant whose major receptor is chemokine receptor 2 (CCR2). In this study, we investigated the role of MCP-1 in BOS using a heterotopic trachea transplant model. C57/B6 mice were recipients of tracheas from either BALB/c (trachea allografts) or C57/B6 mice (syngeneic tracheas). Trachea allografts demonstrated a marked increase in MCP-1 that correlated with mononuclear cell recruitment, CCR2 expression, and collagen deposition. To determine whether MCP-1 was directly involved in mediating BOS, we used a genetic approach using CCR2 −/− mice. Trachea allografts from CCR2 −/− mice showed a marked reduction in hydroxyproline levels at day 21 and day 28 as compared to allografts from CCR2 +/+ mice. Furthermore, there was a marked reduction in mononuclear phagocytes in allografts from CCR2 −/− vs CCR2 +/+ mice, which was not accompanied by a reduction in lymphocytes. This supports the notion that MCP-1 recruits mononuclear phagocytes expressing CCR2 that are phenotypically profibrotic and important in the pathogenesis of BOS.

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