RGD Reference Report - Critical role for the chemokine MCP-1/CCR2 in the pathogenesis of bronchiolitis obliterans syndrome. - Rat Genome Database

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Critical role for the chemokine MCP-1/CCR2 in the pathogenesis of bronchiolitis obliterans syndrome.

Authors: Belperio, JA  Keane, MP  Burdick, MD  Lynch JP, 3RD  Xue, YY  Berlin, A  Ross, DJ  Kunkel, SL  Charo, IF  Strieter, RM 
Citation: Belperio JA, etal., J Clin Invest. 2001 Aug;108(4):547-56.
RGD ID: 4145124
Pubmed: PMID:11518728   (View Abstract at PubMed)
PMCID: PMC209398   (View Article at PubMed Central)
DOI: DOI:10.1172/JCI12214   (Journal Full-text)

Bronchiolitis obliterans syndrome (BOS) is the major limitation to survival after lung transplantation. Acute rejection, its main risk factor, is characterized by perivascular/bronchiolar leukocyte infiltration. BOS is characterized by persistent peribronchiolar leukocyte recruitment leading to airway fibrosis and obliteration. The specific mechanism(s) by which these leukocytes are recruited are unknown. Because MCP-1, acting through its receptor CCR2, is a potent mononuclear cell chemoattractant, we hypothesized that expression of this chemokine during an allogeneic-response promotes persistent recruitment of leukocytes and, ultimately, rejection. We found that elevated levels of biologically active MCP-1 in human bronchial lavage fluid (BALF) were associated with the continuum from acute to chronic allograft rejection. Translational studies in a murine model of BOS demonstrated increased MCP-1 expression paralleling mononuclear cell recruitment and CCR2 expression. Loss of MCP-1/CCR2 signaling, as seen in CCR2(-/-) mice or in WT mice treated with neutralizing antibodies to MCP-1, significantly reduced recruitment of mononuclear phagocytes following tracheal transplantation and led to attenuation of BOS. Lymphocyte infiltration was not reduced under these conditions. We suggest that MCP-1/CCR2 signaling plays an important role in recruitment of mononuclear phagocytes, a pivotal event in the pathogenesis of BOS.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
bronchiolitis obliterans  ISOCcr2 (Mus musculus)4145124; 4145124mRNA:increased expression:trachea:RGD 
bronchiolitis obliterans  IEP 4145124mRNA:increased expression:trachea:RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ccr2  (C-C motif chemokine receptor 2)

Genes (Mus musculus)
Ccr2  (C-C motif chemokine receptor 2)

Genes (Homo sapiens)
CCR2  (C-C motif chemokine receptor 2)


Additional Information