REGULATION OF MACROPHAGE FUNCTION BY COMPONENTS OF WOODSMOKE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 木材烟雾（WS）是根据美国环保署的空气质量指南，这是基于城市颗粒物的研究。 木材烟雾颗粒物与城市颗粒物不同，但WS的具体健康影响尚未确定。 各种研究发现，在使用生物质燃烧（即木材）作为烹饪方法的家庭中，儿童急性呼吸道疾病（ARI）增加。 人类的观察指出了烟雾暴露和呼吸道疾病之间的密切联系，但缺乏所涉及的细胞和分子事件。相比之下，香烟烟雾（CS）的研究是广泛的。 最近的研究已经将CS与芳香烃受体（AhR）的激活及其随后的NF B家族转录因子的RelB成员的激活联系起来。 AhR是一种孤儿受体，与二恶英和二恶英样化合物结合，可以促进免疫系统的改变。 几个小组已经描述了WS中的多种类型的多环芳烃（PAH），其与CS中发现的那些相同或相似。 我们建议使用小鼠肺模型评估WS组分对巨噬细胞功能的影响。 将通过流式细胞术、分子生物学、转基因和无效小鼠品系以及体外功能测定来确定木烟雾引起的巨噬细胞功能改变。我们建议测试的中心假设，即巨噬细胞功能的差异调节的组成部分，木材烟雾通过芳烃受体和NF B途径。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Wood smoke (WS) is regulated according to the EPA guidelines for air quality, which are based on urban particulate studies. Wood smoke particulates are not the same as urban particulates, but the specific health effects of WS are not defined. A variety of studies have found increases in acute respiratory illnesses (ARI) in children in homes where biomass burning (i.e. wood) is the method of cooking. Human observations point to strong links between smoke exposure and respiratory illness, but are lacking in the cellular and molecular events that are involved. By contrast, cigarette smoke (CS) research is extensive. Recent studies have linked CS with activation of the aryl hydrocarbon receptor (AhR) and its subsequent activation of the RelB member of the NF¿B family of transcription factors. AhR is an orphan receptor that binds with dioxin and dioxin-like compounds and can promote alterations in the immune system. Several groups have described multiple types of polyaromatic hydrocarbons (PAH) in WS that are the same or similar to those found in CS. We propose to assess the effects of WS components on macrophage function using a murine pulmonary model. Wood smoke-derived alterations in macrophage function will be defined by flow cytometry, molecular biology, transgenic and null mouse strains, and in vitro functional assays. We propose to test the central hypothesis that macrophage function is differentially regulated by components of wood smoke via the aryl hydrocarbon receptor and NF¿B pathway.