PULMONARY INTERTITIAL DISEASE BY HAPTENS

这项建议的目的是研究 使用简单化学物质(2，4，6， 三硝基-L-氯苯、二硝基氟苯)。 研究中使用的半抗原类似于化学物质(偏三甲苯 酸酐，TMA)被描述为工人在 塑料工业。这些研究针对的是分析 肺间质疾病的实验模型 是由首席调查员开发的。这些研究的结果 研究将有助于理解以下机制 由工业或环境引起的肺部疾病 像半抗原一样反应的化学物质。动物们将被准备好 通过皮肤的半抗原和肺部的反应将会引起 通过气管内接种免疫化学物质。这个 反应将通过肺组织学检查进行分析 组织切片，通过肺灌洗细胞的差异分析， 更重要的是，通过与其他生物化学参数相关的 肺间质纤维化模型。两个肺 已经描述了反应。一个早期的毒性损伤以及一个 晚期病变表现为纤维化改变。 (仓鼠)激发后15-21天取肺。肺免疫 反应将在不同的淋巴隔间进行研究。 阿龙。系统免疫系统的研究将通过量化 具有增殖和延迟型的特异性T淋巴细胞 超敏反应和细胞毒性细胞分析以及定量 血清抗体和特异性抗体形成细胞(AFC)。这个 增强的自然杀伤细胞活性与 肺部疾病将被考虑。这些研究的结果 研究将对免疫机制提供新的见解 参与肺间质疾病的病因学研究。非 实验性(半抗原诱导)肺的免疫机制 疾病将通过开发生物化学定义来确定 肺部病变的特征。初步研究表明 肺总胶原蛋白的增加以及肺组织中 每摩尔胶原蛋白的交联量 实验仓鼠，与仅挑战或正常相比 动物。还收集了数据，记录了随着 实验仓鼠肺中的弹性蛋白(两周后 挑战)与控制动物相比。生化分析 这种肺损伤可以由严重的 免疫动物的免疫挑战将补充 组织学研究，并可能拓宽我们对 一般情况下，肺纤维化的发展。

The purpose of this proposal is to study the expression of hypersensitivity in the lung using simple chemicals (2, 4, 6, trinitro-l-chlorobenzene, TNCB; Dinitrofluorobenezene, DNFB). Haptens used in the studies are similar to chemicals (trimellitic anhydride, TMA) described as industrial hazards of workers in the plastics industry. The studies are directed toward the analysis to experimental models for pulmonary interstitial disease that have been developed by the Principal Investigator. The results of these studies will have relevance for understanding mechanisms for pulmonary disease caused by industrial or environmental chemicals that react like haptens. The animals will be primed with hapten via the skin and a pulmonary response will be elicited by intratracheal inoculation of the immunizing chemical. The reactions will be assayed by histological examination of lung tissue sections, by differential analysis of cells from lung lavage, and importantly by biochemical parameters associated with other models of pulmonary interstitital fibrosis. Two pulmonary reactions have been described. An early toxic lesion as well as a late lesion demonstrating fibrotic changes was observed in (hamster) lungs 15-21 days after challenge. Pulmonary immune responses will be studied in various lymphoid compartments of the lung. The systemic immune system will be studies by quantitating specific T-lymphocytes with proliferation, and delayed type hypersensitivity and cytotoxic cell assays as well as quantitating serum antibody and specific antibody forming cells (AFC). The relationship of augmented natural killer cell activity to the pulmonary disease will be considered. The results from these studies will give new insights into the immune mechanisms that participate in the etiology of pulmonary interstitial disease. Non immune mechanisms of the experimental (hapten induced) lung disease will be determined by developing a biochemical definition of the pulmonary lesion. Preliminary studies have demonstrated an increase in total lung collagen as well as an increase in the amount of crosslinking molecules per mole of collagen in experimental hamster when compared to challenge only or normal animals. Data has also been collected that records as increase in elastin in the lungs of experimental hamsters (two weeks post challenge) compared to control animals. A biochemical analysis of this pulmonary lesion that can be induced by a severe immunological challenge in immune animals will complement the histological studies and may broaden our understanding of the development of fibrosis in the lung in general.