de Boer J Daan, Yang Jack, van den Boogaard Florry E, Hoogendijk Arie J, de Beer Regina, van der Zee Jaring S, Roelofs Joris J T H, van 't Veer Cornelis, de Vos Alex F, van der Poll Tom
Center of Infection and Immunity Amsterdam & Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
J Innate Immun. 2014;6(2):219-26. doi: 10.1159/000354984. Epub 2013 Oct 18.
Mast cells are implicated in allergic and innate immune responses in asthma, although their role in models using an allergen relevant for human disease is incompletely understood. House dust mite (HDM) allergy is common in asthma patients. Our aim was to investigate the role of mast cells in HDM-induced allergic lung inflammation.
Wild-type (Wt) and mast cell-deficient Kit(w-sh) mice on a C57BL/6 background were repetitively exposed to HDM via the airways.
HDM challenge resulted in a rise in tryptase activity in bronchoalveolar lavage fluid (BALF) of Wt mice, indicative of mast cell activation. Kit(w-sh) mice showed a strongly attenuated HDM- induced recruitment of eosinophils in BALF and lung tissue, accompanied by reduced pulmonary levels of the eosinophil chemoattractant eotaxin. Remarkably, Kit(w-sh) mice demonstrated an unaltered capacity to develop lung pathology and increased mucus production in response to HDM. The increased plasma IgE in response to HDM in Wt mice was absent in Kit(w-sh) mice.
These data contrast with previous reports on the role of mast cells in models using ovalbumin as allergen in that C57BL/6 Kit(w-sh) mice display a selective impairment of eosinophil recruitment without differences in other features of allergic inflammation.
肥大细胞参与哮喘的过敏和先天性免疫反应,尽管其在使用与人类疾病相关的变应原的模型中的作用尚未完全明确。屋尘螨(HDM)过敏在哮喘患者中很常见。我们的目的是研究肥大细胞在HDM诱导的过敏性肺部炎症中的作用。
将C57BL/6背景的野生型(Wt)和肥大细胞缺陷型Kit(w-sh)小鼠经气道反复暴露于HDM。
HDM激发导致Wt小鼠支气管肺泡灌洗液(BALF)中类胰蛋白酶活性升高,表明肥大细胞被激活。Kit(w-sh)小鼠BALF和肺组织中HDM诱导的嗜酸性粒细胞募集明显减弱,同时肺组织中嗜酸性粒细胞趋化因子eotaxin水平降低。值得注意的是,Kit(w-sh)小鼠对HDM诱导的肺部病理改变和黏液分泌增加的能力未改变。Kit(w-sh)小鼠对HDM刺激后Wt小鼠中出现的血浆IgE升高无反应。
这些数据与之前关于肥大细胞在以卵清蛋白作为变应原的模型中的作用的报道形成对比,因为C57BL/6 Kit(w-sh)小鼠表现出嗜酸性粒细胞募集的选择性受损,而在过敏性炎症的其他特征方面无差异。