T-CELLS AND ALVEOLAR MACROPHAGES IN ASBESTOS EXPOSURE

石棉暴露中的 T 细胞和肺泡巨噬细胞

• 批准号: 3250493
• 负责人: NANCY L. SPRINCE
• 金额: $ 14.7万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-07-01 至 1989-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3250493
• 关键词: T lymphocyte; X ray spectrometry; affinity chromatography; alveolar macrophages; antibody specificity; asbestos; cellular immunity; cellular pathology; density gradient ultracentrifugation; diagnostic respiratory lavage; drug administration rate /duration; flow cytometry; fluorescence microscopy; human subject; immunoregulation; longitudinal human study; lung imaging /visualization /scanning; lung neoplasms; mesothelioma; monoclonal antibody; occupational disease /disorder; pathologic process; phagocytosis; phase contrast microscopy; pneumoconiosis; pollution related respiratory disorder; prostaglandins; pulmonary fibrosis /granuloma; questionnaires; radiography; respiratory disorder diagnosis; respiratory function; respiratory toxin; scanning electron microscopy; scintillation spectrometry; statistics /biometry

Asbestos-related diseases are a major public health problem in the United States. An estimated 14 million individuals have been exposed to asbestos during their working lives. Asbestos has been causally linked to interstitial lung disease, pleural fibrosis, lung cancer, mesothelioma and cancers of the gastrointestinal tract, larynx and possibly kidney. Preliminary studies suggest that altered immunoregulation may play a role in the pathogenesis of asbestos-related diseases. Preliminary findings of increased OKT4+/OKT8+ ratio in peripheral blood of patients with pleural plaques or asbestosis of the lung and increased OKT8+ in lung tissue of patients with idiopathic pulmonary fibrosis suggest compartmental shifts of circulating T8 bearing lymphocytes into tissue. Preliminary findings of decreased natural killer activity in peripheral blood of subjects with asbestos exposure suggest decreased immune surveillance which may be related to carcinogenicity of asbestos. The aim of this prospective exposure control study is to evaluate further the prevalence of abnormalities of the cellular immune system in asbestos workers and to relate those abnormalities to extent of asbestos exposure and to the presence of asbestos-related diseases. Subjects with low and moderate to high asbestos exposure and normal controls will be evaluated. The investigation will characterize lymphocytes and macrophages by virtue of their reactivity with monoclonal antibodies and by measurements of cell function. With respect to lymphocytes, in vitro natural killer activity will be assessed as will immunoglubin production. With respect to macrophages, assessment of phagocytosis, fibronectin and secretion of soluble mediators will be performed in lung lavage fluid. As an index of asbestos exposure, ferruginous body and asbestos fiber counts will be performed on lung lavage fluid. Fibers will be characterized by elemental analysis and scanning electron microscopy to elucidate fiber type and composition. Serial changes in the immune findings will be correlated with extent of exposure and with clinical manifestations and progression of disease. Statistical methods to be used are one-way analysis of variance, contingency table analysis, multiple linear regression, and longitudinal multivariate analysis. This study will test the validity of measurements of immunity as an index of severity of clinical disease and extent of asbestos exposure.

石棉相关疾病是美国的一个主要公共卫生问题 States. 估计有1400万人接触石棉 在他们的工作生活中。 阿斯伯格综合征与 间质性肺病、胸膜纤维化、肺癌、间皮瘤和 胃肠道、喉癌，可能还有肾癌。 初步研究表明，改变免疫调节可能发挥作用， 石棉相关疾病的发病机制。 的初步结果 胸膜炎患者外周血OKT 4 +/OKT 8+比值升高 斑块或石棉肺和增加OKT 8+在肺组织中， 特发性肺纤维化患者提示 循环携带T8的淋巴细胞进入组织。 的初步结果 受试者外周血中自然杀伤细胞活性降低 石棉暴露表明免疫监视能力下降， 与石棉的致癌性有关。 这一前景的目标 暴露控制研究是为了进一步评估 石棉工人的细胞免疫系统异常， 将这些异常与石棉暴露的程度和 存在与石棉有关的疾病。 受试者中， 将评估高石棉暴露和正常对照。 的 研究将通过以下方法来表征淋巴细胞和巨噬细胞： 它们与单克隆抗体的反应性以及通过测量细胞 功能 对于淋巴细胞，体外自然杀伤活性 将评估免疫球蛋白的产生。 相对于 巨噬细胞，吞噬作用，纤连蛋白和分泌的评估 可溶性介质将在肺灌洗液中进行。 作为指标 石棉暴露，含铁体和石棉纤维计数将 肺灌洗液进行的。 纤维将以元素为特征 分析和扫描电子显微镜来阐明纤维类型， 混合物. 免疫结果的一系列变化将与 暴露程度以及临床表现和进展 疾病 使用的统计方法为单因素方差分析， 列联表分析，多元线性回归，纵向 多变量分析 本研究将测试测量的有效性 免疫力作为临床疾病严重程度和 石棉暴露