Division of Pulmonary Medicine, Allergy and Rheumatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Morioka, Japan.
Int J Rheum Dis. 2013 Aug;16(4):455-62. doi: 10.1111/1756-185X.12075. Epub 2013 May 28.
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.
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.
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.
IM-suppressed pulmonary vascular remodeling in a murine model of allergic vasculitis with eosinophil infiltration.
甲磺酸伊马替尼（IM）是一种有效的、特异性的酪氨酸抑制剂，已有报道称其可抑制肺纤维化中的间质细胞增殖。本研究旨在观察伊马替尼对卵白蛋白（OVA）致敏伴嗜酸性粒细胞浸润的过敏性血管炎小鼠模型血管重构的影响。
C57BL/6 小鼠用卵白蛋白（OVA）和氢氧化铝致敏。阳性对照组每日雾化 OVA 暴露 7 天。OVA 暴露的伊马替尼治疗组每日同时雾化 OVA 暴露 7 天，同时给予伊马替尼治疗。第 7 天，行支气管肺泡灌洗（BAL），取肺组织进行病理学分析。进行细胞分类计数，测量 BAL 液（BALF）中细胞因子的浓度。根据血管炎严重程度标准，对肺动脉的病理变化进行半定量分析。采用 Ki-67 免疫组化检测增殖细胞。
与阳性对照组相比，伊马替尼治疗组 BALF 中的嗜酸性粒细胞数量显著减少。阳性对照组和伊马替尼治疗组 BAL 液中白细胞介素（IL）-2、IL-4、IL-5、干扰素（IFN）-γ、肿瘤坏死因子（TNF）-α、转化生长因子（TGF）-β或血小板衍生生长因子的浓度无显著差异。与 OVA 暴露后对照组相比，伊马替尼治疗组血管炎的病理评分和管腔内 Ki-67 阳性细胞的比值均显著降低。
伊马替尼抑制了卵白蛋白致敏伴嗜酸性粒细胞浸润的过敏性血管炎小鼠模型的肺血管重构。
