Pivotal role of CCR1-positive leukocytes in bleomycin-induced lung fibrosis in mice

J Immunol. 2000 Mar 1;164(5):2745-51. doi: 10.4049/jimmunol.164.5.2745.

Abstract

We have investigated the involvement of chemokine receptor CCR1-positive cells in bleomycin-induced lung injury, a model of pulmonary fibrosis. After bleomycin challenge in C57BL/6J mice, the expression of CCR1 mRNA increased and peaked at day 7, which paralleled to the expression of its ligands, macrophage-inflammatory protein-1 alpha and RANTES. Immunohistochemical study showed that CCR1-positive cells accumulated in the interstitial inflammatory site. Furthermore, the treatment of anti-CCR1 Ab significantly reduced the accumulation of inflammatory cells and collagen deposition, resulting in dramatic improvement of survival. These results suggest that CCR1-positive cells play significant roles in the pathogenesis of pulmonary fibrosis subsequent to bleomycin-induced lung injury, and that CCR1 could be a novel molecular target for intervention therapy against pulmonary fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bleomycin / toxicity*
  • Cell Movement / immunology
  • Female
  • Immune Sera / administration & dosage
  • Injections, Intravenous
  • Leukocytes / immunology
  • Leukocytes / metabolism*
  • Leukocytes / pathology
  • Mice
  • Mice, Inbred C57BL
  • Pulmonary Fibrosis / chemically induced*
  • Pulmonary Fibrosis / immunology*
  • Pulmonary Fibrosis / pathology
  • Pulmonary Fibrosis / prevention & control
  • Rabbits
  • Receptors, CCR1
  • Receptors, Chemokine / biosynthesis
  • Receptors, Chemokine / blood
  • Receptors, Chemokine / immunology
  • Receptors, Chemokine / physiology*

Substances

  • Ccr1 protein, mouse
  • Immune Sera
  • Receptors, CCR1
  • Receptors, Chemokine
  • Bleomycin