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

^* 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; 120:2S)

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.

Footnotes

Abbreviations: BOS = bronchiolitis obliterans syndrome; CCR2 = chemokine receptor 2; MCP = monocyte chemoattractant protein

Supported by National Institutes of Health grants P50HL56402, P50HL6028, and HL03906.

Dr. Belperio is the recipient of a Glaxo Wellcome fellowship award.

This Article Full Text (PDF) Free Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to My Personal Article Archive Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Belperio, J. A. Articles by Strieter, R. M. Search for Related Content PubMed Articles by Belperio, J. A. Articles by Strieter, R. M.