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Effects of imatinib mesylate on pulmonary allergic vasculitis in a murine model
Author(s) -
Suzuki Naomi,
Sasaki Nobuhito,
Utsumi Yu,
Nagashima Hiromi,
Nakamura Yutaka,
Yamashita Masahiro,
Yamauchi Kohei,
Sawai Takashi
Publication year - 2013
Publication title -
international journal of rheumatic diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.795
H-Index - 41
eISSN - 1756-185X
pISSN - 1756-1841
DOI - 10.1111/1756-185x.12075
Subject(s) - medicine , imatinib mesylate , bronchoalveolar lavage , eosinophil , pathology , pulmonary fibrosis , fibrosis , vasculitis , ovalbumin , tumor necrosis factor alpha , immunology , lung , imatinib , immune system , asthma , disease , myeloid leukemia
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 C57 BL /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.