Haley P J, Pavia K F, Swafford D S, Davila D R, Hoover M D, Finch G L
Inhalation Toxicology Research Institute, Lovelace Biomedical and Environmental Research Institute, Albuquerque, New Mexico 87185.
Immunopharmacol Immunotoxicol. 1994 Nov;16(4):627-44. doi: 10.3109/08923979409019743.
Inhalation of beryllium (Be) may result in an immune-mediated, chronic granulomatous pulmonary disorder known as chronic beryllium disease (CBD). The physicochemical form of Be may affect the incidence and severity of CBD. We exposed cynomolgus monkeys, by bronchoscopic, intrabronchiolar instillation, to either beryllium oxide (BeO; heat-treated at 500 degrees C) or Be metal at concentrations selected to achieve equimolar concentrations of available Be2+ ions dissolving from the particles. Monkeys underwent bronchoalveolar lavage of the right and left diaphragmatic lobes at 14, 30, 60, 90, and 120 days post exposure (dpe). Monkeys were sacrificed at 80 and 180 dpe for evaluation of histopathological pulmonary changes. Numbers of lymphocytes from lung lobes of Be metal-exposed, but not BeO-exposed, monkeys were increased at 14, 30 and 90 dpe. Lung lymphocytes were increased for BeO exposed monkeys only at 60 dpe. In vitro, Be-specific, lung lymphocyte proliferation occurred at 14, 60, and 90 dpe for lymphocytes from Be metal-exposed lung lobes only. At no time were values from BeO-exposed lung lobes different from values from control lobes. Lung lesions in Be metal-exposed monkeys were characterized by focally intense, interstitial fibrosis, marked Type II cell hyperplasia, and variable lymphocyte infiltration. Some Be-metal-exposed monkeys had discrete immune granulomas consisting of tightly organized lymphocytic cuffs surrounding nodular aggregates of epithelioid macrophages. Lesions were rarely present in BeO-exposed monkeys and were much less severe. These data suggest that Be metal produces more severe pulmonary lesions than does BeO and that these lesions are accompanied by Be-specific immune responses.
吸入铍（Be）可能导致一种免疫介导的慢性肉芽肿性肺部疾病，称为慢性铍病（CBD）。铍的物理化学形式可能会影响CBD的发病率和严重程度。我们通过支气管镜下支气管内滴注，将食蟹猴暴露于氧化铍（BeO；在500摄氏度下热处理）或铍金属中，所选用的浓度能使从颗粒中溶解的Be2+离子达到等摩尔浓度。在暴露后14、30、60、90和120天（dpe），对猴子的左右膈叶进行支气管肺泡灌洗。在80和180 dpe时处死猴子，以评估肺部组织病理学变化。在14、30和90 dpe时，暴露于铍金属而非BeO的猴子肺叶中的淋巴细胞数量增加。仅在60 dpe时，暴露于BeO的猴子肺淋巴细胞数量增加。在体外，仅来自暴露于铍金属肺叶的淋巴细胞在14、60和90 dpe时出现铍特异性肺淋巴细胞增殖。暴露于BeO的肺叶的值在任何时候都与对照叶的值没有差异。暴露于铍金属的猴子的肺部病变特征为局灶性强烈的间质纤维化、明显的II型细胞增生和可变的淋巴细胞浸润。一些暴露于铍金属的猴子有离散的免疫肉芽肿，由围绕上皮样巨噬细胞结节状聚集物紧密组织的淋巴细胞袖口组成。暴露于BeO的猴子很少出现病变，且严重程度要低得多。这些数据表明，铍金属比BeO产生更严重的肺部病变，并且这些病变伴随着铍特异性免疫反应。
