MODULATION OF ALLERGIC INFLAMMATION BY PASSIVE CIGARETTE SMOKING IN CHILDREN

儿童被动吸烟对过敏性炎症的调节

• 批准号: 6106511
• 负责人: DAVID DIAZ-SANCHEZ
• 金额: $ 22.76万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-11-01 至 1999-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6106511
• 关键词: air pollution; airborne allergen; antigen antibody reaction; chemokine; child (0-11); clinical research; genetic susceptibility; human subject; immunoglobulin E; inflammation; laboratory rat; passive smoking; respiratory disorder epidemiology; respiratory function; smoke inhalation; tobacco abuse

This project will determine the mechanisms by which environmental tobacco smoke (ETS) modify defined phases of the human allergic response in children. Epidemiological data suggests that parental smoking is a major risk factor for allergic sensitization. We will determine the in vivo biological effects of ETS on the induction and enhancement of the specific allergic airway response under clinically relevant conditions and dissect the cellular and molecular mechanisms involved. We will use inhalation challenges in adults and children to define directly how ETS exposure either induces d novo and/or exacerbates ongoing allergic inflammation in the human airway. These human studies will be complemented with animal studies which will answer key genetic and developmental issues that can not be addressed as rigorously in humans. Aim #1 will determine the mechanisms by which ETS alters the in vivo IgE antibody response in the human upper airway. We will determine if ETS directly alters IgE production from mucosal B cells (by inducing germ line transcription or isotype switching) or if it acts indirectly by modifying the airway mucosal environment (by inducing cytokine production or cell surface receptors). Aim #2 will determine if exposure to ETS alters IgE- independent inflammatory responses in the human upper airway by increasing chemokine production (MCP-1, MCP-3, MIP-1alpha, RANTES and eotaxin) or their ability of increasing cellular infiltration and activation. Both of these aims will rely on ETS inhalation challenge studies on groups of allergic non-asthmatic children and adults. Aim #3 will test the hypothesis that the in vivo allergic antibody response due to chronic exposure to ETS is controlled by genetic background and age by using an established animal model. Our studies integrate with Dr. Gong since we will collaborate in the actual ETS inhalation challenges using his exposure chamber at his site. Our work will provide new insights into environmental effects of childhood allergic disease by performing direct experimentation to answer questions previously studied by solely epidemiologic means.

该项目将确定环境烟草的机制 烟雾（ETS）改变了人类过敏反应的定义阶段 孩子们。流行病学数据表明，父母吸烟是主要的 过敏致敏的危险因素。我们将确定体内 ETS 对诱导和增强特异性的生物学效应 临床相关条件下的过敏性气道反应并解剖 所涉及的细胞和分子机制。我们将使用吸入法 成人和儿童面临的挑战是直接定义 ETS 暴露方式 诱导新的和/或加剧持续的过敏性炎症 人体呼吸道。这些人类研究将得到动物研究的补充 将回答关键遗传和发育问题的研究 在人类中不应该受到严格的对待。目标#1将决定 ETS 改变体内 IgE 抗体反应的机制 人类上呼吸道。我们将确定 ETS 是否直接改变 IgE 粘膜 B 细胞的产生（通过诱导种系转录或 同型转换）或通过改变气道间接起作用 粘膜环境（通过诱导细胞因子的产生或细胞表面 受体）。目标 #2 将确定接触 ETS 是否会改变 IgE- 通过增加人类上呼吸道的独立炎症反应 趋化因子产生（MCP-1、MCP-3、MIP-1α、RANTES 和嗜酸细胞趋化因子）或 它们增加细胞浸润和激活的能力。两者都 这些目标将依赖于 ETS 吸入挑战研究 过敏性非哮喘儿童和成人。目标 #3 将测试 假设体内过敏性抗体反应是由于慢性 ETS 的暴露是通过遗传背景和年龄来控制的 建立动物模型。我们的研究与龚博士融为一体，因为我们 将利用他的能力在实际的 ETS 吸入挑战中进行合作 他所在地点的暴露室。我们的工作将提供新的见解 通过直接执行儿童过敏性疾病的环境影响 实验来回答以前单独研究的问题 流行病学手段。