Inhaled Brevetoxins: Health Effects and Mechanisms

吸入短尾毒素：健康影响和机制

基本信息

批准号：
7645750
负责人：
JANET M. BENSON
金额：
$ 25.42万
依托单位：
UNIVERSITY OF NORTH CAROLINA WILMINGTON
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/7645750
关键词：
Accident and Emergency department Address Alveolar Macrophages Antibody Formation Antibody Suppression Antigen-Presenting Cells Antigens Breathing Cathepsins Complex Mixtures Development Erythrocytes Exposure to Health Humoral Immunities Immune Immunization Infection Influenza Inhalation Exposure Investigation Light Lymphocyte Mediating Modeling Mus Perinatal Perinatal Exposure Pneumonia Population Range Rattus Recovery Reporting Role Sheep Spleen T-Lymphocyte Toxic effect Virus Diseases Visit aged brevetoxin immunotoxicity in utero insight macrophage red tide response young adult

Accident and Emergency department Address Alveolar Macrophages Antibody Formation Antibody Suppression Antigen-Presenting Cells Antigens Breathing Cathepsins Complex Mixtures Development Erythrocytes Exposure to Health Humoral Immunities Immune Immunization Infection Influenza Inhalation Exposure Investigation Light Lymphocyte Mediating Modeling Mus Perinatal Perinatal Exposure Pneumonia Population Range Rattus Recovery Reporting Role Sheep Spleen T-Lymphocyte Toxic effect Virus Diseases Visit aged brevetoxin immunotoxicity in utero insight macrophage red tide response young adult

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项目摘要

The major focus of this Project has been to examine the potential adverse health effects resulting from prolonged inhalation exposure to brevetoxins. The inhalation toxicities of a complex mixture of brevetoxins and brevetoxin antagonists in K. brevis extract was examined in rats, and the toxicity of pure brevetoxin 3 was examined in both rats and mice. Substantial immune suppression in rats, as indicated by a reduction in antibody response to immunization with sheep red blood cells, was consistently the primary response observed. Suppression of antibody forming responses occurred in the absence of frank toxicity to the spleen, changes in lymphocyte populations, or T cell responses to antigen. This immune suppression is important in light of reports in increased emergency room visits for pneumonia during Red Tide episodes identified by Fleming project and decreases in alveolar macrophage function in sheep inhaling brevetoxins in project by Abraham. This proposal will address the following specific aims: (1) To define exposure concentration-response relationships for brevetoxin-induced effects on humoral immunity in rats and to examine the role of macrophage cathepsin inhibition in mediating these effects; (2) To examine the effects of brevetoxin inhalation on recovery from infection in a rat model of influenza including young adult and aged rats; and (3) To determine the immunotoxic potential of brevetoxin in offspring of dams inhaling brevetoxins. These investigations will broaden examination of the exposure concentration-response relationship for brevetoxin-induced effects on antibody responses to antigen, provide insight into the underlying mechanism(s) for the observed immune suppression, examine potential consequences to brevetoxin-induced immune suppression on responses to viral infection; and determine the potential developmental immunotoxicity resulting from perinatal brevetoxin exposure.

该项目的主要重点是检查潜在的不良健康影响由于长时间吸入对Brevetoxins的暴露而产生的。复杂混合物的吸入毒性在大鼠中检查了K. brevis提取物中的Brevetoxin和Brevetoxin拮抗剂，纯净的毒性在大鼠和小鼠中检查了Brevetoxin 3。大鼠的实质性免疫抑制，如减少对绵羊红细胞免疫反应的抗体反应，始终是主要的回应观察到。在没有坦率的毒性的情况下，发生抗体形成反应的抑制脾脏，淋巴细胞种群的变化或T细胞对抗原的反应。这种免疫抑制是鉴于在红潮情节期间急诊室就诊时增加的报告很重要通过弗莱明（Fleming）项目鉴定，并在亚伯拉罕（Abraham）的绵羊吸入BrevEtoxins中的肺泡巨噬细胞功能下降。这建议将解决以下特定目的：（1）定义暴露浓度 - 响应关系对于brevetoxin诱导的对大鼠体液免疫的影响，并检查巨噬细胞组织蛋白酶的作用抑制介导这些影响；（2）检查Brevetoxin吸入对从流感大鼠模型中的感染包括年轻大鼠和老年大鼠；（3）确定免疫毒性 Brevetoxin在吸入Brevetoxins的后代的潜力。这些调查将扩大检查Brevetoxin诱导抗体对抗原抗体反应的影响的暴露浓度响应关系，提供了对观察到的免疫抑制的潜在机制的见解，检查对Brevetoxin诱导的免疫抑制对病毒感染的反应的潜在后果；并确定围产期核毒素暴露引起的潜在发育免疫毒性。