Effects of imatinib mesylate on pulmonary allergic vasculitis in a murine model

Authors

  • Naomi Suzuki,

    1. Division of Pulmonary Medicine, Allergy and Rheumatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Morioka, Japan
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  • Nobuhito Sasaki,

    1. Division of Pulmonary Medicine, Allergy and Rheumatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Morioka, Japan
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  • Yu Utsumi,

    1. Division of Pulmonary Medicine, Allergy and Rheumatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Morioka, Japan
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  • Hiromi Nagashima,

    1. Division of Pulmonary Medicine, Allergy and Rheumatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Morioka, Japan
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  • Yutaka Nakamura,

    1. Division of Pulmonary Medicine, Allergy and Rheumatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Morioka, Japan
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  • Masahiro Yamashita,

    1. Division of Pulmonary Medicine, Allergy and Rheumatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Morioka, Japan
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  • Kohei Yamauchi,

    Corresponding author
    1. Division of Pulmonary Medicine, Allergy and Rheumatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Morioka, Japan
    • Correspondence: Professor Kohei Yamauchi, Division of Pulmonary Medicine, Allergy and Rheumatology, Department of Internal Medicine, Iwate Medical University School of Medicine, 19–1 Uchimaru, Morioka 020–8505, Japan.

      Email: kyamauch@iwate-med.ac.jp

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  • Takashi Sawai

    1. Department of Pathology, Iwate Medical University School of Medicine, Morioka, Japan
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Abstract

Objectives

Imatinib mesylate (IM) is a potent and specific tyrosine inhibitor and has been reported to inhibit mesenchymal cell proliferation in pulmonary fibrosis. In the present study, we examine the effects of IM on vascular remodeling in a murine model of allergic vasculitis with eosinophil infiltration.

Methods

C57BL/6 mice were sensitized with ovalbumin (OVA) and alum. The positive controls were exposed to aerosolized OVA daily for 7 days. IM treated mice with exposure to OVA were administered IM in parallel with daily exposure to aerosolized OVA for 7 days. On the 7th day, bronchoalveolar lavage (BAL) was performed and the lungs were excised for pathological analysis. Cell differentials were determined and the concentrations of cytokines in the BAL fluid (BALF) were measured. Semi-quantitative analysis of pathological changes in the pulmonary arteries was evaluated according to the criteria of severity of vasculitis. Immunohistochemistry for Ki-67 to detect proliferating cells was performed.

Results

The number of eosinophils in BALF was reduced significantly in the IM-treated group compared to the positive control. There was no significant difference in the concentrations of interleukin (IL)-2, IL-4, IL-5, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, tumor growth factor (TGF)-β or platelet-derived growth factor in the BAL fluid between the positive control and the IM-treated group. The pathological scores of vasculitis and the ratio of Ki-67-positive intra-luminal cells were reduced significantly in the IM-treated group compared to the control group after OVA exposure.

Conclusion

IM-suppressed pulmonary vascular remodeling in a murine model of allergic vasculitis with eosinophil infiltration.

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