HETEROGENEITY OF RESIDENT ALVEOLAR MACROPHAGE

驻留肺泡巨噬细胞的异质性

• 批准号: 3074098
• 负责人: RICHARD T SAWYER
• 金额: $ 5.27万
• 依托单位: MERCER UNIVERSITY MACON
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-03-01 至 1991-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3074098
• 关键词: Candida albicans; Corynebacterium; Listeria; alveolar macrophages; antigens; cell growth regulation; cell population study; cell type; colony stimulating factor; disease /disorder model; endotoxins; flow cytometry; genetic strain; interferons; laboratory mouse; leukopenia; monoclonal antibody; phagocytes; radiotracer; surface antigens

The experimental model proposed in this study is designed to resolve fundamental questions concerning the existance of functional subsets among resident pulmonary alveolar macrophages (PAM). The study will take advantage of the strontium-89 (89Sr) monocytopenic mouse model which provides for the analysis of resident PAM surface marker heterogeneity in the absence of contamination by emigrating monocyte-macrophage. The objective of this study is to establish the existance of PAM subsets among resident PAM populations, in the absence of monocytes, and to evaluate the ability of those subsets to selectively increase their cell numbers in response to inflammatory stimuli. PAM subset heterogeneity and proliferative activity will be compared and contrasted in normal, outbred mice and in genetically defective inbred strains of mice. Flow cytometry will be used to characterize the subset distribution of a variety of monoclonal antibodies (MABs) to epitopes on the surface of mononuclear phagocytes. 125I-MAB binding studies will measure the number of MABs/PAM while propidium iodide staining will be employed to evaluate the cell cycle times of PAM subsets by flow cytometry. Upon defining a battery of subset-specific MABs, subsets will be sorted by fluoresence activated cell sorting and the cell cycle times measured for each subset. ICR mice will be challenged in vivo, with Candida albicans, Corynebacterium parvum, Listeria monocytogenes, endotoxin, alpha interferon or with macrophage growth factor (CSF-1), and the effects of challenge on PAM subset surface markers and subset proliferation determined. Similar studies will be performed in C57B1/6bgbg, C3H/HeJ, C3H/HeN, PN, W/Wv, and SLSLd inbred mouse strains. The objective of this study is to determine if alterations in the expression of PAM subset surface epitopes correlate with changes in proliferative capacity.

本研究提出的实验模型旨在解决 关于功能子集存在的基本问题 常驻肺泡巨噬细胞（PAM）。 该研究将采取 锶 89 (89Sr) 单核细胞减少小鼠模型的优点 提供驻留 PAM 表面标记异质性分析 不存在迁移的单核巨噬细胞的污染。 这 本研究的目的是确定 PAM 子集的存在 常驻 PAM 群体，在没有单核细胞的情况下，并评估 这些子集选择性增加其细胞数量的能力 对炎症刺激的反应。 PAM 子集异质性和 增殖活性将在正常、远交中进行比较和对比 小鼠和有遗传缺陷的近交系小鼠。 流式细胞术将用于表征子集分布 针对表面表位的多种单克隆抗体 (MAB) 单核吞噬细胞。 125I-MAB 结合研究将测量数量 MABs/PAM，同时使用碘化丙啶染色来评估 通过流式细胞术测量 PAM 亚群的细胞周期时间。 定义一个 一组特定于子集的 MAB，子集将按荧光排序 激活细胞分选并测量每个子集的细胞周期时间。 ICR小鼠将在体内受到白色念珠菌、棒状杆菌的挑战 微小颗粒、单核细胞增多性李斯特菌、内毒素、α干扰素或与 巨噬细胞生长因子 (CSF-1) 以及挑战对 PAM 的影响 确定子集表面标记和子集增殖。 相似的 研究将在 C57B1/6bgbg、C3H/HeJ、C3H/HeN、PN、W/Wv 和 SLSLd 近交小鼠品系。 本研究的目的是确定是否 PAM 子集表面表位表达的改变与 增殖能力的变化。