A critical role for CCR2/MCP-1 interactions in the development of idiopathic pneumonia syndrome after allogeneic bone marrow transplantation

Blood. 2004 Mar 15;103(6):2417-26. doi: 10.1182/blood-2003-08-2708. Epub 2003 Nov 13.


Idiopathic pneumonia syndrome (IPS) is a major complication after allogeneic bone marrow transplantation (allo-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 chemokine receptor 2 (CCR2) and its primary ligand monocyte chemoattractant protein-1 (MCP-1). To test this hypothesis, IPS was induced in a lethally irradiated parent --> F1 mouse BMT model. Compared with 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 with transplantation of wild-type (CCR2+/+) cells and in reduced bronchoalveolar lavage (BAL) fluid cellularity and BAL fluid levels of tumor necrosis factor-alpha (TNF-alpha) and soluble p55 TNF receptor (sTNFRI). In addition, neutralization of MCP-1 resulted in significantly decreased lung injury compared with 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bone Marrow Transplantation / adverse effects*
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology
  • Chemokine CCL2 / metabolism*
  • Cytokines / metabolism
  • Female
  • Lung / immunology
  • Lung / pathology
  • Macrophages / immunology
  • Macrophages / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Monocytes / immunology
  • Monocytes / pathology
  • Pneumonia / immunology*
  • Pneumonia / metabolism*
  • Pneumonia / pathology
  • RNA, Messenger / metabolism
  • Receptors, CCR2
  • Receptors, Chemokine / genetics
  • Receptors, Chemokine / metabolism*
  • Severity of Illness Index
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology
  • Transplantation, Homologous


  • Ccr2 protein, mouse
  • Chemokine CCL2
  • Cytokines
  • RNA, Messenger
  • Receptors, CCR2
  • Receptors, Chemokine