Laboratory Recognition of Potential Xenobiotic Respiratory Sensitizers

M. Ward, C. Pucheu-Haston
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Abstract

The immune system functions to establish and maintain homeostasis to protect the body from infectious agents and certain tumours. However, the interaction between the immune system and some xenobiotics can perturb this homeostasis, resulting in adverse health events, including the development of hypersensitivity reactions in genetically predisposed individuals. The dramatic increase in protein-induced respiratory hypersensitivity in the USA and other industrialized nations over the last few decades is presumably the result of changes in environment, lifestyle and/or medical practices. This chapter provides an overview of selected laboratory methods used in the identification and health-risk assessment of potential respiratory sensitizers. We describe animal models of hypersensitivity that have been used to elucidate disease pathogenesis and hazard identification. Methods for animal exposure, sample collection and end-point assessment are also discussed. In addition to in vivo models, the development of in vitro screening techniques and the utility of technologies such as protein and gene expression microarrays, PCR and multiplexing systems in hazard screening are also described. The models and methods discussed in this chapter have been used in our laboratory and others, not only to determine the risks associated with bioaerosol exposure, but also to elucidate disease mechanism and potential intervention targets. Keywords: hypersensitivity; allergy; hypersensitivity pneumonitis; animal models; cell culture
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潜在的异种呼吸致敏剂的实验室识别
免疫系统的功能是建立和维持体内平衡,以保护身体免受传染病和某些肿瘤的侵害。然而,免疫系统和一些外源性药物之间的相互作用会扰乱这种体内平衡,导致不良健康事件,包括遗传易感个体的超敏反应的发展。在过去的几十年里,美国和其他工业化国家中蛋白质引起的呼吸道过敏的急剧增加可能是环境、生活方式和/或医疗实践变化的结果。本章概述了用于识别和评估潜在呼吸道致敏物健康风险的实验室方法。我们描述过敏的动物模型,已用于阐明疾病的发病机制和危害识别。还讨论了动物接触、样本收集和终点评估的方法。除了体内模型外,还介绍了体外筛选技术的发展以及诸如蛋白质和基因表达微阵列、PCR和多路复用系统等技术在危害筛选中的应用。本章讨论的模型和方法已经在我们的实验室和其他实验室中使用,不仅可以确定与生物气溶胶暴露相关的风险,还可以阐明疾病机制和潜在的干预目标。关键词:超敏反应;过敏;过敏性肺炎;动物模型;细胞培养
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