IMMUNE RESPONSIVENESS IN CHLORINE EXPOSED RATS

急性、亚致命刺激性气体暴露的幸存者可能 出现持续的长期呼吸道症状和/或 功能障碍。这些症状可能是由 增强了对抗原的敏感性。炎症是该病的标志 刺激性气体损伤与许多表面上的区别 观察到的是与行动地点有关的，这是由 刺激物的物理/化学性质，而不是固有的 回应上的差异。氯被广泛使用， 经常涉及工业或交通事故，以及 具有中等的溶解度；因此，它可以发挥其主要的 呼吸道各部分的影响。既然有目的 人类暴露在高浓度的氯中永远不可能 在这项提案中，有理由认为下列长期呼吸影响是合理的 氯气暴露将在动物模型中进行评估。 Fisher 344大鼠将暴露在氯气中，并呈剂量依赖关系 时尚；这将确保诱发一系列亚致命伤害。 氯气暴露对免疫反应性的影响 被评估。仅通过鼻部暴露，老鼠将被致敏 不同间隔(2小时、1小时、7小时、30小时、 和60天)。在敏化到 将对骨关节炎、局部和全身抗体反应进行量化 使用酶联免疫吸附试验和被动 皮肤过敏反应测试。评估蜂窝网络 反应性，淋巴细胞转化，使用分离的细胞 取脾、肺相关淋巴结行培养 对于骨性关节炎或刀豆球蛋白A，将进行手术。 本提案中概述的实验旨在检验 氯暴露的结果，但结果可能适用于 对其他主要刺激物的共同致病作用 机制，和/或呼吸道和肺部炎症。如果 这些发现表明，对特定疾病的易感性增加 敏感化，这将为研究设计提供指导 或对暴露的工作计划的监视计划。

Survivors of an acute, sub-lethal irritant gas exposure may present with persistent long-term respiratory symptoms and/or functional impairment. These symptoms may result from enhanced sensitivity to antigen. Inflammation is the hallmark of irritant gas injury and many of the superficial differences observed are related to the site of action, which is determined by physical/chemical properties of the irritant, rather than intrinsic differences in the response. Chlorine is widely used and frequently involved in industrial or transportation accidents, and has intermediate solubility; therefore, it may exert its primary effects of all portions of the respiratory tract. Since purposeful exposure of humans to high levels of chlorine could never be justified, in this proposal, long-term respiratory effects following chlorine exposure will be evaluated in an animal model. Fisher 344 rats will be exposed to chlorine gas, in dose-dependent fashion; this will ensure induction of a range of sub-lethal injuries. The effects of chlorine exposure on immune responsiveness, will be evaluated. Rats will be sensitized, by nose-only exposure, to aerosolized ovalbumin (OA), at various intervals (2 hr, 1, 7, 30, and 60 days) post-chlorine exposure. Following sensitization to OA, local and systemic antibody responses will be quantitated using an enzyme linked immunosorbent assay and passive cutaneous anaphylaxis testing. To evaluate cellular responsiveness, lymphocyte transformation, using cells isolated from the spleen and the lung associated lymph nodes, and cultured with OA or concanavalin A will be performed. The experiments outlined in this proposal are designed to examine the outcome of chlorine exposure, but the results will likely apply to other primary irritants by virtue of their common pathogenetic mechanisms, and/or respiratory tract and lung inflammation. If the findings indicate enhanced susceptibility to specific sensitization, this would provide guidance in the design of studies or surveillance programs for exposed working programs.