OCCUPATIONAL AFLATOXICOSIS

职业性黄曲霉毒素中毒

• 批准号: 2517368
• 负责人: GEORGE J JAKAB
• 金额: $ 18.83万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-01 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2517368
• 关键词: Haemophilus influenzae; Klebsiella pneumoniae; Listeria; T lymphocyte; aflatoxins; antigen presenting cell; cellular immunity; dust; grain; immunosuppression; immunotoxicity; laboratory rat; lung injury; occupational hazard; respiratory infections; Haemophilus influenzae; Klebsiella pneumoniae; Listeria; T lymphocyte; aflatoxins; antigen presenting cell; cellular immunity; dust; grain; immunosuppression; immunotoxicity; laboratory rat; lung injury; occupational hazard; respiratory infections

DESCRIPTION (Adapted from the Applicant's Abstract): Surveys have shown that AFB1 is frequently found in respirable grain dust (up to 43,700 ppb) and that the serum of occupational workers exposed to contaminated dust contains AFB1-albumin adducts. The investigators' data demonstrate that respiratory exposure of rodents to AFB1 impairs the alveolar macrophage (AM) phagocytic defense system. The results indicate that respiratory exposure to AFB1 should be considered a human health risk is associated with diseases resulting from impaired lung defenses where exposure to AFB1-laden dusts is common. Indeed, through its effect on lowered lung resistance, AFB1 exposure poses a more wide ranging and insidious health hazard than its genotoxic endpoint. It is well established that oral exposure to AFB1 impairs a wide spectrum of systemic host defenses however, the mechanism of this effect have not been addressed. The observation that oral AFB1 Impairs the antibody response to a T-dependent antigen but not to a T-independent antigen provides a clue to the mechanism by indicating that AFB1 has an effect on T-lymphocytes. Critical to the evaluation of the magnitude of human risk from inhalation of AFB1-contaminated grain dust is an experimental data base. However, the full biologic effect of respiratory exposure to AFB1 on lung defenses is not known nor are the mechanisms involved. The goal of the proposed research is to define the cellular mechanisms of AFB1-induced suppression of pulmonary defenses and elucidate the consequences of such impairments. The overall hypothesis of this application is that respiratory AFB1 exposure regulates the innate and acquired immune responses though alterations of the functional capacity of the antigen presenting cells, and the T-lymphocyte repertoire of the immune response. Also, data-response relationships between inhalation to AFB1- laden grain dust that estimate occupational exposure and the most sensitive parameters of altered immune response will define the no effect level. These studies will establish the experimental data base required for the development of a risk assessment model of human populations exposed to AFB1-contaminated grain dust. This data base can then be used as a guide to focus epidemiologic studies toward a more complete assessment of the health hazard of occupational inhalation exposure to AFB1-laden grain dust.

描述（根据申请人的摘要改编）：调查已显示 AFB1经常在可呼吸的谷物灰尘（最多43,700 ppb）和暴露于受污染的职业工人的血清 灰尘含有AFB1-α金合蛋白加合物。 调查人员的数据证明了 啮齿动物对AFB1的呼吸道暴露会损害肺泡 巨噬细胞（AM）吞噬防御系统。 结果表明 呼吸道暴露于AFB1应被视为人类健康风险 与肺部防御受损产生的疾病有关 暴露于含有AFB1的灰尘很常见。 确实，通过其对 降低肺阻力，AFB1暴露构成更宽的范围 阴险的健康危害比其遗传毒性终点。 众所周知，口腔暴露于AFB1会损害广泛的范围 但是，系统性宿主防御措施，这种效果的机制尚未 已解决。 口服AFB1损害抗体的观察结果 对T依赖性抗原的反应，但对T独立抗原的反应 通过表明AFB1具有效果，提供了该机制的线索 在T淋巴细胞上。 对吸入的人类风险的评估至关重要 AFB1污染的谷物尘是一个实验数据库。 然而， 呼吸道暴露于AFB1对肺的完整生物学作用 防御尚不清楚，涉及机制。 目标的目标 拟议的研究是定义AFB1诱导的细胞机制 抑制肺部防御并阐明这种后果 障碍。 该应用程序的总体假设是 呼吸道AFB1暴露调节先天并获得的免疫 响应尽管改变了抗原的功能能力 呈现细胞和免疫的T淋巴细胞库 回复。 此外，吸入到AFB1-之间的数据响应关系 估计职业曝光和最多的谷物灰尘 改变免疫反应的敏感参数将定义无效 等级。 这些研究将确定用于的实验数据库 开发暴露于人口的风险评估模型 AFB1污染的谷物灰尘。 然后可以将此数据库用作指南 将流行病学研究重点放在更完整的评估 职业吸入暴露于AFB1谷物的健康危害 灰尘。