A Study on Immunotoxicity in Animal Models for Metal Lung

本研究旨在通过动物模型阐明镍、钴引起的过敏性肺病的发病机制。首先，采用气管内注入超细镍或钴颗粒的方法建立大鼠间质性肺炎模型。与石英或超细二氧化钛相比，含镍的模型表现出持久而严重的肺泡炎和间质性肺炎。此外，镍模型在进展期可见淋巴细胞浸润。在镍和钴肺模型中，肿瘤坏死因子和包括一氧化氮和超氧化物在内的活性氧在持续炎症中起作用。同时，建立了皮肤钴致敏的豚鼠模型。结果表明，肺泡巨噬细胞可促进自体胸腔淋巴结淋巴细胞的体外增殖。提示皮肤致敏豚鼠模型有可能导致呼吸道钴暴露致肺超敏反应模型。综上所述，本研究建立了大鼠和豚鼠金属染毒模型，为进一步了解镍肺和钴肺的发病机制提供了依据。

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.