The Role of Osteopontin in the Development of Granulomatous Lesions in Lung

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  • Chiba Satoru
    Section of Immunopathogenesis, Institute of Immunological Science, Hokkaido University Department of Cardiovascular Medicine, Hokkaido University Medical School
  • Rashid Mohammod Mizanur
    Section of Immunopathogenesis, Institute of Immunological Science, Hokkaido University
  • Okamoto Hiroshi
    Department of Cardiovascular Medicine, Hokkaido University Medical School
  • Shiraiwa Hirotake
    Section of Immunopathogenesis, Institute of Immunological Science, Hokkaido University
  • Kon Shigeyuki
    Section of Immunopathogenesis, Institute of Immunological Science, Hokkaido University
  • Maeda Masahiro
    Immuno-Biological Laboratories
  • Murakami Masaaki
    Section of Immunopathogenesis, Institute of Immunological Science, Hokkaido University
  • Inobe Manabu
    Section of Immunopathogenesis, Institute of Immunological Science, Hokkaido University
  • Kitabatake Akira
    Department of Cardiovascular Medicine, Hokkaido University Medical School
  • Chambers Ann F.
    The London Regional Cancer Centre
  • Uede Toshimitsu
    Section of Immunopathogenesis, Institute of Immunological Science, Hokkaido University

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  • Role of Osteopontin in the Development of Granulomatous Lesions in Lung

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Abstract

Osteopontin (OPN) has been shown to be expressed by cells in granulomas of various origins, but whether it plays a functional role in granuloma formation is not known. Here we used a cardiomyopathic hamster (TO2) model, to test the hypothesis that OPN contributes functionally to granuloma development. We immunized cardiomyopathic and normal hamsters by subcutaneous injection of bovine serum albumin in complete Freund's adjuvant, and assessed various tissues for both OPN RNA expression and granuloma formation. Cardiomyopathic hamsters expressed OPN, and formed granulomatous lesions, in heart tissue in both immunized and untreated animals. In addition, immunization induced expression of OPN in lung and lymph nodes of cardiomyopathic (but not normal) hamsters, and also induced granuloma formation in these organs. To test whether OPN expression could play a functional role in inducing granulomas, we produced an adenoviral vector containing the murine OPN gene, and introduced this vector intratracheally into the lungs of normal hamsters. The OPN-containing vector, but not the control vector, induced pulmonary granuloma formation. These studies provided direct in vivo evidence that OPN can contribute functionally to the formation of granulomatous lesions, and suggest that OPN expression maybe a common factor involved in formation of granulomas of various origin.

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