MURINE CRD: A MODEL OF CHRONIC PULMONARY IMFLAMMATION

我们的实验室已经做了很多工作来解释病因学和 一种自然发生的慢性呼吸道疾病的发病机制 大鼠和小鼠呼吸道支原体病(MRM) 由肺支原体引起。所有发生的损伤 自然地在MRM中通过接种M. 已知无其他病原体的大鼠，以及一种 利用差异建立了具有高度重复性的模型 在LEW和F344大鼠中表现为疾病易感性。公认的 慢性支气管炎的形态相似和相似的自然历史 人类的呼吸系统疾病和MRM，以及 后者可重现，提供理论依据和实验依据 为利用该模型研究慢性阻塞性肺疾病的发病机制奠定了基础 肺部发炎。 上呼吸道和下呼吸道疾病进展更快 与F344大鼠相比，LEW大鼠的发病速度更快，病情更严重。在……里面 这两种菌株的病变严重程度都与 BALT大小和肺内淋巴细胞总数。 到目前为止获得的数据提出了三个假设 LEW和F344大鼠病变发展的差异。第一 假设这种差异是由淋巴细胞引起的 淋巴趋化导致的浸润性病变。第二个假设是 更高程度的激活(无论是特定的还是非特定的) LOW大鼠皮损内淋巴细胞发生AS 与F344大鼠相比，或者至少在 特异性和非特异性淋巴细胞活化的比率 是存在的。最后，损伤严重程度的差异可能是由于 对这两个菌株的调控影响的差异。它是 重要的是要注意，这些假设并不是相互的 排他性的，这三种可能性实际上都可能起到作用 在病变的演变过程中。在此授权期内，我们的特定 目标是：(I)确定哪些病变是淋巴细胞 调解，(Ii)确定激活和非激活的比率 两株猪肺病变中淋巴细胞及其表型， (Iii)确定LEW和F344大鼠在数量上是否不同 抗肺分支杆菌特异性抗体产生细胞(APC)和总抗体 感染肺中APC的数量，(Iv)确定T细胞是否 在任一菌株的皮损中非特异性激活，(V)确定 如果肺部病变中淋巴细胞数量的差异 LEW和F344大鼠是因为淋巴细胞的差异 募集或克隆扩增，(Vi)鉴定细胞 以及介导炎症渗透的分子信号， 包括淋巴细胞迁移，以及(Vii)确定影响 调节细胞亚群对病变发展的影响， 尤其是高辅助细胞：抑制细胞比率的影响。

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.