Mast cells play a partial role in allergen-induced subepithelial fibrosis in a murine model of allergic asthma
Mast cells play a partial role in allergen-induced subepithelial fibrosis in a murine model of allergic asthma
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DOI：
10.1046/j.1365-2222.2003.01588.x
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发表时间：
2003-05-01
影响因子：
6.1
通讯作者：
Nagai, H
中科院分区：
文献类型：
--
作者：
Masuda, T;Tanaka, H;Nagai, H
背景肥大细胞在过敏原诱导的气道重塑中的作用尚未在体内得到充分的研究。目的为了阐明肥大细胞在过敏原诱导的气道重塑中的可能作用，我们比较了遗传性肥大细胞缺陷小鼠，WBB6F1-W/W-v（c-kit突变体）和Sl/Sl（d）（c-kit配体突变）小鼠与同种正常小鼠在过敏性哮喘小鼠模型中的差异。方法小鼠用卵清蛋白（OA）和明矾致敏，每天暴露于雾化OA，持续3周。结果致敏肥大细胞缺陷小鼠支气管对乙酰胆碱（Ach）的高反应性、支气管肺泡灌洗（BAL）液中炎性细胞数和转化生长因子β 1（TGF β 1）水平均明显低于致敏肥大细胞缺陷小鼠，且支气管肺泡灌洗液中TGF β 1水平明显高于致敏肥大细胞缺陷小鼠。反复过敏原刺激后上皮的IgE反应和杯状细胞增生与同类小鼠无显著差异。与此相反，上皮下纤维化，在气道周围的纤维化区域进行评估，观察同类小鼠反复过敏原的挑战后，部分减弱肥大细胞缺陷小鼠。此外，肥大细胞缺陷小鼠肺中羟脯氨酸的含量显著低于同类小鼠。结论肥大细胞在变应原诱导的上皮下纤维化的发生中起部分作用，尽管反复变应原刺激引起的气道炎症、上皮重塑和BHR与肥大细胞无关，至少在这个模型中。
Background Role of mast cells in the development of allergen-induced airway remodelling has not been fully investigated in vivo .Objective To clarify the possible role of mast cells in the development of allergen-induced airway remodelling, we compared their responses of genetically mast cell-deficient mice, WBB6F1-W/W-v (c-kit mutant) and Sl/Sl(d) (c-kit ligand mutant) mice with those of congenic normal mice in a murine model of allergic asthma.Methods Mice were sensitized to ovalbumin (OA) with alum, and exposed daily for 3 weeks to aerosolized OA. Twenty-four hours after the last inhalation, bronchial responsiveness to acetylcholine (Ach) was measured, and bronchoalveolar lavage (BAL), and biochemical and histological examinations were performed.Results In both sensitized mast cell-deficient mice, the degree of bronchial hyper-responsiveness to Ach, the number of inflammatory cells and the level of transforming growth factor-beta1 in BAL fluid, IgE response and goblet cell hyperplasia in the epithelium after repeated allergen provocation were not significantly different from those of congenic mice. In contrast, subepithelial fibrosis, evaluated in the fibrotic area around the airways, observed in congenic mice after repeated allergen challenge was partially attenuated in both mast cell-deficient mice. In addition, the amount of hydroxyproline in the lung of mast cell-deficient mice was significantly lower than that of congenic mice. Furthermore, the decreased fibrotic area and amount of hydroxyproline in W/W-v mice was completely recovered by reconstitution of tissue mast cells with bone marrow-derived mast cells of congenic mice.Conclusion These findings suggest that mast cells play a partial role in the development of allergen-induced subepithelial fibrosis, although airway inflammation, epithelial remodelling and BHR caused by repeated allergen challenge are independent of mast cells, at least in this model.