Farraj Aimen K, Harkema Jack R, Kaminski Norbert E
Department of Pharmacology and Toxicology and Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI 48824, USA.
Toxicol Sci. 2006 Jul;92(1):321-8. doi: 10.1093/toxsci/kfj191. Epub 2006 Apr 11.
Allergic airway diseases caused by low-molecular weight chemicals including trimellitic anhydride (TMA) have been linked to Th2 cytokines and are characterized by mucus hypersecretion and infiltration of lymphocytes and eosinophils into the airways. The most common route of human exposure to chemical respiratory allergens is inhalation. Most murine models, however, use topical exposure to sensitize mice. The present study tests the hypothesis that topical sensitization on the ears of mice with TMA will induce a qualitatively similar immunologic and pathologic response in the nasal airways after intranasal challenge to that induced after intranasal sensitization and challenge. A/J mice were sensitized topically or by intranasal instillation followed by intranasal challenge with TMA in an ethyl acetate/olive oil vehicle. Intranasal challenge with TMA in mice that were either topically or intranasally sensitized with TMA caused a marked allergic rhinitis, of similar severity, characterized by an influx of eosinophils and lymphocytes. Both the topical and intranasal routes of sensitization also caused significant increases in total serum IgE after intranasal challenge with TMA. In addition, both the topical and intranasal routes of sensitization caused significant increases in the mRNA expression of the Th2 cytokines IL-4, IL-5, and IL-13. Collectively, these findings suggest that topical application is effective in sensitizing mice to TMA and induces a nasal airway lesion and associated immune response after intranasal challenge, which is qualitatively similar to that induced by intranasal sensitization and challenge. Skin exposure may be a potential route of sensitization of the respiratory tract to chemical allergens.
由包括偏苯三酸酐（TMA）在内的低分子量化学物质引起的变应性气道疾病与Th2细胞因子有关，其特征为黏液分泌过多以及淋巴细胞和嗜酸性粒细胞浸润气道。人类接触化学性呼吸道变应原的最常见途径是吸入。然而，大多数小鼠模型采用局部暴露来使小鼠致敏。本研究检验了这样一个假设，即对小鼠耳部进行TMA局部致敏后，经鼻激发所诱导的鼻气道免疫和病理反应在性质上与经鼻致敏和激发后所诱导的反应相似。将A/J小鼠通过局部或经鼻滴注致敏，随后用溶解于乙酸乙酯/橄榄油载体中的TMA进行经鼻激发。用TMA对经局部或经鼻致敏的小鼠进行经鼻激发，会引发明显程度相似的变应性鼻炎，其特征为嗜酸性粒细胞和淋巴细胞流入。TMA经鼻激发后，局部和经鼻致敏途径均导致血清总IgE显著增加。此外，局部和经鼻致敏途径均导致Th2细胞因子IL-4、IL-5和IL-13的mRNA表达显著增加。总体而言，这些发现表明局部应用可有效使小鼠对TMA致敏，并在经鼻激发后诱导鼻气道病变及相关免疫反应，这在性质上与经鼻致敏和激发所诱导的反应相似。皮肤暴露可能是呼吸道对化学变应原致敏的一个潜在途径。
