EFFECTS OF 03 AND N02 ON LUNG MACROPHAGE PHAGOCYTOSIS

03和N02对肺巨噬细胞吞噬功能的影响

• 批准号: 3250779
• 负责人: RALPH J PAROD
• 金额: $ 11.61万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-07-01 至 1986-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3250779
• 关键词: air pollution; alveolar macrophages; calcium; cell age; cyclic AMP; environmental toxicology; flow cytometry; gas analyzer; immunoregulation; inhalation drug administration; opsonin; phagocytosis; pollution related respiratory disorder; radioimmunoassay; radiotracer; respiratory toxin; scintillation counter; scintillation spectrometry; surface antigens

Although some studies suggest that several pollutant gases inhibit pulmonary macrophage phagocytosis, the mechanism mediating this inhibition is unknown. We have developed new techniques to investigate phagocytosis. These include the ability to distinguish and quantitate bound versus ingested particles as well as the ability to evaluate the heterogeneity of these and other characteristics within the pulmonary macrophage population. Using a combination of in vivo and in vitro experiments, we propose to delineate the mechanism by which two pollutant gases, ozone (03) and nitrogen dioxide (NO2) affect the phagocytosis of immunologically unopsonized particles. In one series of experiments we will evaluate the effects of 03 and N02 on the phagocytic capability of individual macrophages within the exposed cell population. The uptake of green fluorescent latex particles coated with albumin will be quantitated using flow cytometry. The differentiation of attached versus ingested particles will be made utilizing rhodamine conjugated antibodies to the particle surface. We will also evaluate the effects of these gases on the age distribution of resident macrophages. Macrophage age will be determined by quantitating the amount of an age-related cell surface antigen specific to pulmonary macrophages. Since both gases elicit an inflammatory response, another series of experiments will evaluate the effects of inflammatory agents on phagocytosis. These agents will be used to explore the roles of intracellular calcium and cyclic cAMP in phagocytosis and will facilitate our continuing effort to define factors which regulate phagocytic function. The integration of this information will enhance our understanding of how phagocytosis is affected in vivo by pollutant gases and other inflammatory agents.

虽然一些研究表明，一些污染气体抑制 肺巨噬细胞吞噬作用，介导这种抑制的机制 不明 我们已经开发了研究吞噬作用的新技术。 这些包括区分和定量结合与 摄入的颗粒以及评估 肺巨噬细胞内的这些和其他特征 人口 使用体内和体外实验的组合，我们 建议描述两种污染气体，臭氧（03） 和二氧化氮（NO2）影响免疫细胞的吞噬作用 未调理的颗粒。 在一系列实验中，我们将评估 03和N02对个体吞噬能力的影响 暴露的细胞群中的巨噬细胞。 对绿色的吸收 用白蛋白包被的荧光乳胶颗粒将使用 流式细胞仪 附着颗粒与摄入颗粒的区别 将利用罗丹明结合的颗粒抗体 面 我们还将评估这些气体对年龄的影响 常驻巨噬细胞的分布。 巨噬细胞年龄将通过 定量特异于以下的年龄相关细胞表面抗原的量： 肺巨噬细胞 因为两种气体都会引起炎症反应， 另一系列的实验将评估炎症的影响， 对吞噬作用的影响。 这些代理人将被用来探索的作用， 细胞内钙和环cAMP在吞噬作用中，并将促进 我们不断努力确定调节吞噬细胞的因子， 功能 这些信息的整合将增强我们的 了解体内吞噬作用如何受污染气体影响 和其他炎症因子。