Kinetics of macrophage subpopulations and expression of monocyte chemoattractant protein-1 (MCP-1) in bleomycin-induced lung injury of rats studied by a novel monoclonal antibody against rat MCP-1

Y. Sakanashi, M. Takeya, T. Yoshimura, L. Feng, T. Morioka, K. Takahashi

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We investigated the kinetics of macrophage subpopulations and the expression of monocyte chemoattractant protein 1 (MCP-1) in a rat model of bleomycin-induced lung injury. Rat macrophage subpopulations were examined by immunohistochemistry using various anti-rat macrophage monoclonal antibodies (mAbs) and their proliferative capacity by [3H]thymidine (3HTdR) autoradiography. To detect the localization of expressed MCP-1, we generated an mAb against rat MCP-1 for immunohistochemical staining. Expression of MCP-1 messenger RNA (mRNA) was detected by Northern blot hybridization. Shortly after intratracheal instillation of bleomycin, the number of exudate macrophages recognized by mAb TRPM-3 increased in the injured lungs, peaked 3 days later, and decreased thereafter, whereas tissue macrophages identified by mAb ED2 increased slowly and peaked 2 weeks after instillation. Northern blot analysis disclosed that the expression of MCP-1 mRNA in the lung was most prominent 1 day after instillation and declined thereafter, preceding the numerical change of the TRPM-3-positive exudate macrophages. Immunohistochemistry with anti-rat MCP-1 revealed that the main sources of MCP-1 production were alveolar and interstitial macrophages and polymorphonuclear leukocytes. Based on these results, MCP-1 produced by polymorphonuclear leukocytes and by alveolar and interstitial macrophages is thought to induce the infiltration of blood monocytes, and infiltrated exudate macrophages produce MCP-1 to enhance subsequent accumulation of macrophages. In contrast, the expression of MCP-1 did not correlate with the numerical changes of the ED2-positive macrophages.

Original languageEnglish
Pages (from-to)741-750
Number of pages10
JournalJournal of Leukocyte Biology
Issue number6
Publication statusPublished - Dec 1 1994
Externally publishedYes



  • Autoradiography
  • Immunohistochemistry
  • Northern blot hybridization

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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