Immunoglobulin E antibodies enhance pulmonary inflammation induced by inhalation of a chemical hapten.
Immunoglobulin E antibodies enhance pulmonary inflammation induced by inhalation of a chemical hapten.
复制标题
免疫球蛋白 E 抗体可增强吸入化学半抗原引起的肺部炎症。
DOI：
10.1111/j.1365-2222.2008.03140.x
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Oettgen,HC
中科院分区：
文献类型：
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作者：
Mathias,CB;Freyschmidt,E-J;Oettgen,HC
职业接触化学品是哮喘的一个重要原因。最近的研究表明，IgE抗体增强了皮肤对化学物质的敏感性。目的探讨接触致敏剂吸入后IgE是否同样促进气道炎症的发展。方法建立化学诱导哮喘模型，通过呼吸道引入低分子量化合物三硝基苯磺酸（TNBS）进行致敏和致敏。通过比较野生型（WT）和IgE缺陷型（IgE−/−）小鼠在BALB/c背景下的免疫反应，评估了IgE抗体在该模型中对吸入TNBS的免疫反应中的作用。在致敏前，通过静脉注射IgE抗体重建IgE - / -小鼠的循环IgE水平，以证实IgE在WT和IgE - / -小鼠的反应中所观察到的差异中的作用。结果经鼻刺激致敏的TNBS小鼠（而非假致敏的对照组小鼠）引起强烈的肺部炎症。巨噬细胞、嗜酸性粒细胞和淋巴细胞（包括T细胞、B细胞、自然杀伤细胞和自然杀伤T细胞）被招募到气道，动物对甲胆碱表现出支气管高反应性（BHR）。小鼠血清肥大细胞蛋白酶- 1 （mMCP - 1）水平升高，提示肥大细胞活化。相反，在IgE‐缺乏的小鼠中，气道炎症的发展、淋巴细胞的募集、BHR的诱导和mMCP‐1的产生都明显减弱。在致敏前用IgE（不相关抗原特异性）重建IgE - / -小鼠部分恢复了哮喘的这些特征。结论我们的数据表明，IgE抗体非特异性地促进暴露于化学抗原诱导的气道炎症的发展。
BackgroundOccupational exposure to chemicals is an important cause of asthma. Recent studies indicate that IgE antibodies enhance sensitization to chemicals in the skin.ObjectiveWe investigated whether IgE might similarly promote the development of airway inflammation following inhalation of a contact sensitizer.MethodsA model of chemical‐induced asthma is described in which introduction of the low‐molecular‐weight compound, trinitrobenzene sulphonic acid (TNBS), via the respiratory tract was used for both sensitization and challenge. The role of IgE antibodies in the immune response to inhaled TNBS in this model was assessed by comparing the responses of wild‐type (WT) and IgE‐deficient (IgE−/−) mice on the BALB/c background. Reconstitution of circulating IgE levels by intravenous injection of IgE antibodies into IgE−/−mice before sensitization was performed to confirm the role of IgE in any differences observed between the responses of WT and IgE−/−mice.ResultsIntranasal challenge of TNBS‐sensitized (but not sham‐sensitized control mice) induced intense pulmonary inflammation. Macrophages, eosinophils and lymphocytes, including T, B, natural killer and natural killer T cells, were recruited to the airway and the animals displayed bronchial hyperresponsiveness (BHR) to methacholine. Serum levels of murine mast cell protease‐1 (mMCP‐1) were elevated suggesting mast cell activation. In contrast, the development of airway inflammation, recruitment of lymphocytes, induction of BHR and production of mMCP‐1 were all significantly attenuated in IgE‐deficient mice. Reconstitution of IgE−/−mice with IgE (of unrelated antigen specificity) before sensitization partially restored these features of asthma.ConclusionOur data indicate that IgE antibodies non‐specifically enhance the development of airway inflammation induced by exposure to chemical antigens.