Mapp C E, Lapa e Silva J R, Lucchini R E, Chitano P, Rado V, Saetta M, Pretolani M, Karol M H, Maestrelli P, Fabbri L M
Institute of Occupational Medicine, University of Padova, Italy.
Am J Respir Crit Care Med. 1996 Jul;154(1):201-8. doi: 10.1164/ajrccm.154.1.8680681.
Toluene diisocyanate (TDI)-induced asthma is a common cause of occupational lung disease. We used a model to investigate the course of bronchopulmonary inflammation following immunization with TDI. Guinea pigs were immunized by weekly intradermal injections and challenged with TDI 7 d after the third injection. The animals were killed at different times after challenge and prepared for histologic examination of central and peripheral airways, for immunohistochemical studies of T lymphocyte and eosinophil distribution, and for hematologic and serologic investigations. Specific IgG1 against TDI were present only in immunized animals. In immunized TDI-challenged animals there was a significant increase in the number of metachromatic cells (at 24 h) and a late increase of eosinophils (at 48 h) in the peripheral blood. Mast cells and eosinophils were also increased in the submucosa of central airways of immunized TDI-challenged animals. A similar pattern was observed in the animals' peripheral airways. Additionally, a significant increase of T-lymphocytes and eosinophils was found in the lamina propria at 6 h after exposure in immunized TDI-challenged animals as compared with control animals. In these immunized animals, TDI challenge caused a significant increase of eosinophils, T-lymphocytes, and CD4+ T cells. These findings indicate that intradermal injections of TDI induced a specific antibody response as well as an inflammatory process in both central and peripheral airways. T cells, particularly CD4+ T cells and eosinophils, are the key cells in the immunopathologic alterations induced by TDI in the guinea pig lung.
甲苯二异氰酸酯（TDI）诱发的哮喘是职业性肺病的常见病因。我们使用一种模型来研究用TDI免疫后支气管肺炎症的病程。通过每周皮内注射对豚鼠进行免疫，并在第三次注射后7天用TDI进行激发。在激发后的不同时间处死动物，制备用于中央和外周气道组织学检查、T淋巴细胞和嗜酸性粒细胞分布免疫组织化学研究以及血液学和血清学调查的样本。仅在免疫动物中存在针对TDI的特异性IgG1。在免疫的TDI激发动物中，外周血中异染细胞数量显著增加（在24小时时），嗜酸性粒细胞数量后期增加（在48小时时）。免疫的TDI激发动物中央气道黏膜下层的肥大细胞和嗜酸性粒细胞也增加。在动物的外周气道中观察到类似模式。此外，与对照动物相比，免疫的TDI激发动物在暴露后6小时固有层中T淋巴细胞和嗜酸性粒细胞显著增加。在这些免疫动物中，TDI激发导致嗜酸性粒细胞、T淋巴细胞和CD4 + T细胞显著增加。这些发现表明皮内注射TDI在中央和外周气道均诱导了特异性抗体反应以及炎症过程。T细胞，尤其是CD4 + T细胞和嗜酸性粒细胞，是TDI诱导豚鼠肺部免疫病理改变的关键细胞。
