A Study on Immunotoxicity in Animal Models for Metal Lung

本研究旨在通过动物模型阐明镍钴致过敏性肺病的机制。首先，用超细镍或钴颗粒建立大鼠间质性肺炎模型。与石英或超细二氧化钛相比，镍模型表现出更严重的持续性肺泡炎和间质性肺炎。此外，镍模型在晚期显示淋巴细胞浸润。在镍和钴肺模型中，肿瘤坏死因子和活性氧（包括一氧化氮和超氧化物）等物质在持续性炎症中发挥作用。同时建立了钴皮肤致敏豚鼠模型。结果表明，肺泡巨噬细胞促进自体胸淋巴结淋巴细胞的体外增殖。提示皮肤致敏豚鼠模型可能导致钴呼吸道暴露的肺超敏反应。因此，本研究建议采用大鼠模型和豚鼠模型对镍肺和钴肺疾病的发病机制进行进一步的研究。

The present study was aimed at clarifying mechanism for hypersensitivity lung disease caused by nickel and cobalt by using animal models. Firstly, the rat model for interstitial pneumonitis was developed with intratracheal instillation of ultrafine nickel or cobalt particles. The model with nickel presented with lasting and severe alveolitis and interstitial pneumonitis to more extent than quartz or ultrafine titanium dioxide. Moreover, the nickel model showed lymphocyte infiltrations at the advance stage. Stockiness such as tumor necrosis factor and reactive oxygen species including nitric oxide and super oxide were revealed to play roles in the persistent inflammation in the both nickel and cobalt lung models. At the same time, a guinea pig model sensitized with skin exposure to cobalt was developed. It was shown that alveolar macrophages enhanced in vitro proliferation of lymphocytes from autologous thoracic lymphnodes. Thus the result suggested a possibility that skin sensitized guinea pig model may lead to pulmonary hypersensitivity model on respiratory exposure to cobalt. Taken together, the rat model and guinea pig model made with exposure to metals were suggested to provide further knowledge on mechanism underlying nickel lung and cobalt lung disease.