MURINE CRD: A MODEL OF CHRONIC PULMONARY IMFLAMMATION

小鼠 CRD：慢性肺部炎症模型

• 批准号: 3335920
• 负责人: GAIL H. CASSELL
• 金额: $ 17.3万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1976
• 资助国家: 美国
• 起止时间: 1976-06-30 至 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3335920
• 关键词: B lymphocyte; Mycoplasma pneumoniae; T lymphocyte; alveolar macrophages; antibody formation; athymic mouse; autoradiography; bacterial antigens; bacterial cytopathogenic effect; bactericidal immunity; biological models; cell motility; cell type; cellular immunity; chronic disease /disorder; delayed hypersensitivity; disease /disorder model; disease /disorder proneness /risk; electron microscopy; host organism interaction; immunoelectron microscopy; immunofluorescence technique; immunopathology; inflammation; laboratory mouse; laboratory rat; leukocyte activation /transformation; lymphatic tissue; microorganism immunology; model design /development; mycoplasmal pneumonia; neutrophil; phagocytes; radiotracer; respiratory hypersensitivity; respiratory infections; serology /serodiagnosis

Much work has been in our laboratory to explain the etiology and pathogenesis of a naturally occurring chronic respiratory disease in rats and mice; murine respiratory mycoplasmosis (MRM) resulting from Mycoplasma pulmonis. All lesions that occur naturally in MRM have been reproduced by inoculation of M. pulmonis into rats known to be free from other pathogens, and a highly reproducible model has been established using differences in LEW and F344 rats in disease susceptibility. The recognized morphologic similarities and similar natural histories of chronic respiratory diseases of man and MRM, and the ease wherewith the latter can be reproduced, provide the rationale and experimental basis for use of this model to study mechanisms in chronic pulmonary inflammation. Both upper and lower respiratory tract disease progress more rapidly and are more severe in LEW as compared to F344 rats. In both strains, the severity of lesions is directly correlated to the size of BALT and the total number of lymphocytes in the lung. The data obtained thus far suggest three hypotheses for the differences in lesion development in LEW and F344 rats. The first hypothesis is that the differences result from lymphocyte infiltration due to lymphoid chemotaxis. The second hypothesis is that a higher degree of activation (either specific or nonspecific) occurs for lymphocytes located in the lesions in LEW rats as compared to those in F344 rats, or at least, that a difference in the ratio between specific and non-specific lymphocyte activation is present. Finally, the differences in lesions severity may be due to differences in the regulatory influences in the two strains. It is important to note that these hypotheses are not mutually exclusive and that all three possibilities may actually play a role in evolution of lesions. During this grant period our specific objectives are to: (i) determine which lesions are lymphocyte mediated, (ii) determine the ratios of activated vs non-activated lymphocytes and their phenotypes in lung lesions of both strains, (iii) determine if LEW and F344 rats differ in the numbers of specific antibody-producing cells (APC) to M. pulmonis and total numbers of APC in infected lungs, (iv) determine if T cells are non-specifically activated in lesions of either strain, (v) determine if differences in the number of lymphocytes in lung lesions of LEW and F344 rats is because of differences in lymphocyte recruitment or their clonal expansion, (vi) identify the cellular and molecular signals that mediate inflammatory infiltration, including lymphocyte immigration, and (vii) determine the effects of regulatory cell subpopulations on lesion development, especially the effects of a high helper:suppressor cell ratio.

我们的实验室已经做了大量工作来解释病因， 自然发生的慢性呼吸道疾病的发病机制 大鼠和小鼠;鼠呼吸道支原体病（MRM） 是由肺支原体引起的 所有发生的病变 在MRM中自然地通过接种M. 肺内感染，已知不含其他病原体， 高度可重复的模型已建立使用差异 LEW和F344大鼠的疾病易感性。 所识别的 形态相似性和慢性病的相似自然史 人的呼吸道疾病和MRM，以及容易与 后者可以复制，提供理论基础和实验依据 使用该模型研究慢性炎症机制的基础 肺部炎症 上呼吸道和下呼吸道疾病进展更多 与F344大鼠相比，LEW中的细胞凋亡迅速且更严重。 在 这两种菌株，病变的严重程度直接相关， BALT的大小和肺中淋巴细胞的总数。 迄今为止获得的数据提出了三种假设， LEW和F344大鼠中病变发展的差异。 第一 一种假说认为，这种差异是由淋巴细胞 由于淋巴趋化性的浸润。 第二个假设是 更高程度的激活（特异性或非特异性） 位于LEW大鼠病变中的淋巴细胞发生， 与F344大鼠相比，或者至少， 特异性和非特异性淋巴细胞活化之间的比率 存在。 最后，病变严重程度的差异可能是由于 两种菌株的调节影响的差异。 是 值得注意的是，这些假设并不相互关联。 所有这三种可能性都可能发挥作用 在病变的演变中。 在此期间，我们的具体 目的是：（i）确定哪些病变是淋巴细胞 介导的，（ii）确定活化与非活化的比率 淋巴细胞及其表型， (iii)确定LEW和F344大鼠在 特异性抗体产生细胞（APC）。肺和总 （iv）确定是否存在T细胞， 在任一菌株的病变中非特异性活化，（v）确定 如果肺损伤中淋巴细胞数量的差异 LEW和F344大鼠淋巴细胞数量的差异 招募或其克隆扩增，（vi）鉴定细胞的 以及介导炎症浸润的分子信号， 包括淋巴细胞迁移，以及（七）确定影响 调节细胞亚群对病变发展的影响， 特别是高辅助细胞：抑制细胞比率的影响。