Haley P J, Finch G L, Mewhinney J A, Harmsen A G, Hahn F F, Hoover M D, Muggenburg B A, Bice D E
Inhalation Toxicology Research Institute, Lovelace Biomedical and Environmental Research Institute, Albuquerque, New Mexico.
Lab Invest. 1989 Aug;61(2):219-27.
Groups of beagle dogs were exposed by inhalation to attain either low or high initial lung burdens (ILB) of BeO calcined at 500 degrees or 1000 degrees C. Dogs were killed at 8, 32, 64, 180, and 365 days after exposure for evaluation of beryllium tissue burdens and histopathologic examination. Histologic lesions were characterized by perivascular and peribronchiolar infiltrates of lymphocytes and macrophages 8 days after exposure. These lesions progressed to distinct microgranulomas accompanied by patchy granulomatous pneumonia. Lesions were more severe in dogs exposed to 500 degrees C BeO. Additional dogs were sampled by bronchoalveolar lavage at 3, 6, 7, 11, 15, 18, and 22 months after exposure for characterization of lung cytology and lung immune responses. Lymphocyte percentages and numbers were increased in lavage samples 3 months after exposure in dogs with both the high and low ILB of 500 degrees C. Values for both parameters decreased rapidly thereafter. Dogs with either low or high ILB of 1000 degrees C-treated BeO displayed negligible to low and variable changes in both lymphocyte percentages and numbers. In vitro lymphocyte stimulation by beryllium was increased 180 and 210 days after exposure in dogs with the high ILB 500 degrees C BeO only. A marked degree of individual variation in both histologic lesions and lymphocyte responses among dogs was noted. Less soluble 1000 degrees C-treated BeO was retained in the lung longer than the more soluble 500 degrees C-treated material that was cleared almost entirely by 1 year after exposure. Because these changes are similar to those reported in humans with chronic beryllium disease, these data suggest that the beagle represents a good model to study histologic and immunologic aspects of this disease syndrome.
将比格犬分组，通过吸入使其达到在500摄氏度或1000摄氏度下煅烧的氧化铍的低或高初始肺负荷（ILB）。在暴露后8、32、64、180和365天处死犬，以评估铍组织负荷并进行组织病理学检查。组织学病变的特征是暴露后8天淋巴细胞和巨噬细胞的血管周围和细支气管周围浸润。这些病变进展为明显的微肉芽肿，并伴有散在的肉芽肿性肺炎。暴露于500摄氏度氧化铍的犬的病变更严重。在暴露后3、6、7、11、15、18和22个月，通过支气管肺泡灌洗对另外的犬进行采样，以表征肺细胞学和肺免疫反应。暴露后3个月，500摄氏度下高ILB和低ILB的犬的灌洗样本中淋巴细胞百分比和数量均增加。此后，这两个参数的值迅速下降。1000摄氏度处理的氧化铍的低或高ILB的犬在淋巴细胞百分比和数量上显示出可忽略不计至低且变化不定的变化。仅在暴露后180和210天，500摄氏度高ILB氧化铍的犬中铍对体外淋巴细胞的刺激增加。注意到犬之间在组织学病变和淋巴细胞反应方面存在明显的个体差异。较难溶解的1000摄氏度处理的氧化铍在肺中保留的时间比较易溶解的500摄氏度处理的材料更长，后者在暴露后1年几乎完全清除。由于这些变化与慢性铍病患者中报道的变化相似，这些数据表明比格犬是研究该疾病综合征的组织学和免疫学方面的良好模型。
