Immune sensitization to methylene diphenyl diisocyanate (MDI) resulting from skin exposure: albumin as a carrier protein connecting skin exposure to subsequent respiratory responses.
Immune sensitization to methylene diphenyl diisocyanate (MDI) resulting from skin exposure: albumin as a carrier protein connecting skin exposure to subsequent respiratory responses.
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DOI：
10.1186/1745-6673-6-6
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发表时间：
2011-03-17
期刊：
影响因子：
--
通讯作者：
Herrick CA
中科院分区：
文献类型：
--
作者：
Wisnewski AV;Xu L;Robinson E;Liu J;Redlich CA;Herrick CA
亚甲基二苯基二异氰酸酯（MDI）是一种用于商业聚氨酯生产的反应性化学品，是公认的职业性哮喘的原因。迄今为止，疾病预防工作的主要重点是呼吸道接触；然而，皮肤暴露也可能是诱导免疫致敏的重要途径，这可能会促进随后的气道炎症反应。我们建立了一个小鼠模型来研究MDI皮肤暴露可能促进后续免疫反应（包括呼吸道炎症）的致病机制。小鼠通过皮肤暴露于不同剂量（0.1-10% w/v）的丙酮/橄榄油稀释的MDI，随后评估MDI的免疫致敏性。采用酶联免疫吸附试验（ELISA）检测血清中mdi特异性IgG和IgE水平，同时采用支气管肺泡灌洗法（BAL）评估经鼻给药mdi -小鼠白蛋白偶联物诱导的呼吸道炎症。使用“仅皮肤”暴露小鼠的自体血清IgG检测和指导体内暴露MDI抗原修饰的皮肤蛋白的纯化/鉴定。皮肤暴露于MDI导致特异性抗体的产生，并促进了鼻内MDI-小鼠白蛋白偶联物引起的呼吸道炎症。（继发性）呼吸道炎症和嗜酸性粒细胞增多的程度取决于（原发性）皮肤暴露剂量，在暴露于1% MDI的小鼠中最大，但矛盾的是，在接受10倍高剂量（例如10% MDI）的小鼠中有限。在局部MDI皮肤暴露部位的主要抗原修饰蛋白被鉴定为白蛋白，并显示出与MDI偶联一致的生物物理变化。MDI皮肤暴露可诱导MDI特异性免疫敏感性，促进随后的呼吸道炎症反应，因此可能在MDI哮喘发病机制中起重要作用。MDI偶联和白蛋白在局部（皮肤/呼吸道）暴露部位的抗原修饰可能代表了皮肤暴露与随后的呼吸道炎症之间的共同抗原环节。
Methylene diphenyl diisocyanate (MDI), a reactive chemical used for commercial polyurethane production, is a well-recognized cause of occupational asthma. The major focus of disease prevention efforts to date has been respiratory tract exposure; however, skin exposure may also be an important route for inducing immune sensitization, which may promote subsequent airway inflammatory responses. We developed a murine model to investigate pathogenic mechanisms by which MDI skin exposure might promote subsequent immune responses, including respiratory tract inflammation. Mice exposed via the skin to varying doses (0.1-10% w/v) of MDI diluted in acetone/olive oil were subsequently evaluated for MDI immune sensitization. Serum levels of MDI-specific IgG and IgE were measured by enzyme-linked immunosorbant assay (ELISA), while respiratory tract inflammation, induced by intranasal delivery of MDI-mouse albumin conjugates, was evaluated based on bronchoalveolar lavage (BAL). Autologous serum IgG from "skin only" exposed mice was used to detect and guide the purification/identification of skin proteins antigenically modified by MDI exposure in vivo. Skin exposure to MDI resulted in specific antibody production and promoted subsequent respiratory tract inflammation in animals challenged intranasally with MDI-mouse albumin conjugates. The degree of (secondary) respiratory tract inflammation and eosinophilia depended upon the (primary) skin exposure dose, and was maximal in mice exposed to 1% MDI, but paradoxically limited in mice receiving 10-fold higher doses (e.g. 10% MDI). The major antigenically-modified protein at the local MDI skin exposure site was identified as albumin, and demonstrated biophysical changes consistent with MDI conjugation. MDI skin exposure can induce MDI-specific immune sensitivity and promote subsequent respiratory tract inflammatory responses and thus, may play an important role in MDI asthma pathogenesis. MDI conjugation and antigenic modification of albumin at local (skin/respiratory tract) exposure sites may represent the common antigenic link connecting skin exposure to subsequent respiratory tract inflammation.
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