Zeiss C R, Leach C L, Smith L J, Levitz D, Hatoum N S, Garvin P J, Patterson R
Department of Medicine, Northwestern University Medical School, Chicago, Illinois.
Am Rev Respir Dis. 1988 Jan;137(1):191-6. doi: 10.1164/ajrccm/137.1.191.
Trimellitic anhydride (TMA) can induce immunologic lung disease in exposed workers. We have developed a rat model of TMA lung injury characterized by lung hemorrhage and an immune response to trimellityl (TM) haptenized lung proteins. The model is similar to the pulmonary disease-anemia syndrome (PDA) seen in workers exposed to TMA fumes. Sprague-Dawley rats, 15 per exposure period, inhaled micronized TMA powder, 100 micrograms/m3, 6 h/day, for 2,6, or 10 days and were sacrificed. At each time period, total, IgG, IgA, and IgM antibody to TM-rat serum albumin (TM-RSA) were measured by radiolabeled antigen binding and enzyme-linked immunosorbent assay (ELISA) in serum and bronchoalveolar lavage fluid (BAL). Hemorrhagic lung foci, weight, and displacement volume were determined, and lungs were examined by light and electron microscopy. There was no lung injury or antibody response at 2 days. There was minimal lung injury at 6 days with low levels of antibody in BAL and serum. At 10 days, there was a marked increase in hemorrhagic foci and in BAL and serum antibody levels. BAL antibody levels at 6 and 10 days had higher correlations with measures of lung injury than corresponding serum levels. There was minimal ultrastructural change at 6 days. By Day 10, there was marked intraalveolar hemorrhage, alveolar septal inflammatory nodules, abundant alveolar macrophages, and evidence of endothelial and epithelial cell injury. These results indicate that the immune response to inhaled TMA occurs parallel with the development of lung lesions, and antibody levels in BAL and serum are highly correlated with lung injury.
偏苯三酸酐（TMA）可使接触该物质的工人罹患免疫性肺部疾病。我们已建立了一种TMA肺损伤大鼠模型，其特征为肺出血以及对经偏苯三甲酰（TM）半抗原化的肺蛋白产生免疫反应。该模型类似于接触TMA烟雾的工人所出现的肺部疾病 - 贫血综合征（PDA）。每组15只Sprague-Dawley大鼠，在每个暴露阶段吸入微粉化的TMA粉末，浓度为100微克/立方米，每天6小时，持续2、6或10天，然后处死。在每个时间段，通过放射性标记抗原结合法和酶联免疫吸附测定（ELISA），检测血清和支气管肺泡灌洗液（BAL）中针对TM - 大鼠血清白蛋白（TM - RSA）的总抗体、IgG、IgA和IgM抗体。测定出血性肺病灶、肺重量和肺容量，并通过光镜和电镜检查肺部。2天时未出现肺损伤或抗体反应。6天时肺损伤轻微，BAL和血清中的抗体水平较低。10天时，出血病灶以及BAL和血清中的抗体水平显著增加。6天和10天时BAL中的抗体水平与肺损伤指标的相关性高于相应的血清水平。6天时超微结构变化轻微。到第10天，出现明显的肺泡内出血、肺泡间隔炎性结节、大量肺泡巨噬细胞以及内皮细胞和上皮细胞损伤的证据。这些结果表明，对吸入TMA的免疫反应与肺部病变的发展同时发生，BAL和血清中的抗体水平与肺损伤高度相关。
