IMMUNE RESPONSIVENESS IN CHLORINE EXPOSED RATS

急性亚致死刺激性气体暴露的幸存者可能 存在持续的长期呼吸道症状和/或 功能障碍 这些症状可能是由于 增强对抗原的敏感性。 炎症是 刺激性气体损伤和许多表面上的差异 观察到的与作用部位有关，这是由 刺激物的物理/化学性质，而不是内在的 答案的差异。 氯被广泛使用， 经常发生工业或交通事故， 具有中等溶解度;因此，它可以发挥其主要的 影响呼吸道的所有部分。 既然有目的 人类暴露在高浓度的氯中， 在本提案中，以下长期呼吸影响是合理的 将在动物模型中评估氯暴露。 将Fisher 344大鼠暴露于氯气中，呈剂量依赖性 时尚;这将确保诱导一系列亚致命伤害。 氯暴露对免疫反应的影响，将 被评价。 大鼠将通过仅鼻暴露致敏， 雾化卵清蛋白（OA），在不同的时间间隔（2小时，1，7，30， 和60天）后的氯暴露。 致敏后， 将定量OA、局部和全身抗体应答 使用酶联免疫吸附测定和被动 皮肤过敏试验 为了评估细胞 反应性，淋巴细胞转化，使用分离的细胞 从脾和肺相关淋巴结中，并培养 将进行OA或伴刀豆球蛋白A。 本提案中概述的实验旨在检查 氯暴露的结果，但结果可能适用于 由于它们共同的致病性， 机制和/或呼吸道和肺部炎症。 如果 研究结果表明，增强的易感性， 这将为研究设计提供指导 或监视暴露的工作程序。

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.