MURINE CRD: A MODEL OF CHRONIC PULMONARY IMFLAMMATION

我们实验室做了很多工作来解释病因和

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.