Masuda T, Tanaka H, Komai M, Nagao K, Ishizaki M, Kajiwara D, Nagai H
Department of Pharmacology, Gifu Pharmaceutical University, Gifu, Japan.
Clin Exp Allergy. 2003 May;33(5):705-13. doi: 10.1046/j.1365-2222.2003.01588.x.
Role of mast cells in the development of allergen-induced airway remodelling has not been fully investigated in vivo.
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/Wv (c-kit mutant) and Sl/Sld (c-kit ligand mutant) mice with those of congenic normal mice in a murine model of allergic asthma.
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.
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/Wv mice was completely recovered by reconstitution of tissue mast cells with bone marrow-derived mast cells of congenic mice.
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.
肥大细胞在变应原诱导的气道重塑发展中的作用尚未在体内得到充分研究。
为阐明肥大细胞在变应原诱导的气道重塑发展中的可能作用，我们在过敏性哮喘小鼠模型中，比较了基因性肥大细胞缺陷小鼠WBB6F1-W/Wv（c-kit突变体）和Sl/Sld（c-kit配体突变体）小鼠与同基因正常小鼠的反应。
用明矾使小鼠对卵清蛋白（OA）致敏，并每天雾化吸入OA 3周。末次吸入后24小时，测量支气管对乙酰胆碱（Ach）的反应性，并进行支气管肺泡灌洗（BAL）以及生化和组织学检查。
在两种致敏的肥大细胞缺陷小鼠中，反复变应原激发后，支气管对Ach的高反应性程度、炎症细胞数量、BAL液中转化生长因子-β1水平、IgE反应以及上皮中杯状细胞增生与同基因小鼠相比均无显著差异。相反，在反复变应原激发后同基因小鼠气道周围纤维化区域观察到的上皮下纤维化，在两种肥大细胞缺陷小鼠中均部分减轻。此外，肥大细胞缺陷小鼠肺中羟脯氨酸含量显著低于同基因小鼠。此外，用同基因小鼠的骨髓源性肥大细胞重建组织肥大细胞后，W/Wv小鼠中减少的纤维化区域和羟脯氨酸含量完全恢复。
这些发现表明，肥大细胞在变应原诱导的上皮下纤维化发展中起部分作用，尽管反复变应原激发引起的气道炎症、上皮重塑和BHR至少在该模型中与肥大细胞无关。
