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.

本研究中提出的实验模型旨在解决 有关在功能子集存在的基本问题 常驻肺肺泡巨噬细胞（PAM）。 该研究将接受 锶89（89SR）单核减少小鼠模型的优势 规定了居民PAM表面标记异质性的分析 通过迁移单核细胞巨噬细胞没有污染。 这 这项研究的目的是建立PAM子集的存在 在没有单核细胞的情况下，居民PAM种群并评估 这些子集选择性增加其单元格的能力 对炎症刺激的反应。 PAM子集异质性和 在正常的，几种中，将比较增生活性并形成鲜明的对比 小鼠和遗传缺陷的小鼠菌株。 流式细胞仪将用于表征A的子集分布 与表面表面的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 将使用碘化丙啶染色时的mAb/pAM进行评估 通过流式细胞术的PAM子集的细胞周期时间。 定义一个 子集特异性mAb电池，子集将通过荧光分类 激活的细胞分选和每个子集测量的细胞周期时间。 ICR小鼠将在体内受到挑战，白色念珠菌，Corynebacterium parvum，李斯特菌单核细胞增生蛋白酶，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 子集表面标记和子集增殖确定。 相似的 研究将在C57B1/6BGBG，C3H/HEJ，C3H/HEN，PN，W/WV和 SLSLD近交小鼠菌株。 这项研究的目的是确定是否 PAM亚群表面表演表达表达的改变与 增殖能力的变化。