Establishment of an Experimental Hypersensitivity Pneumonitis Model in Mice

Abstract

We developed a murine model of hypersensitivity pneumonitis (HP) by repeated transnasal administration of Thermoactinomyces vulgaris (Tv) bacilli. After 3 weeks' exposure diffuse alveolitis with granulomatous lesions was demonstrated in C57Black/6 mice. Anti-Tv-IgG antibodies and delayed-type hypersensitivity against Tv were also detected. Bronchoalveolar lavage (BAL) revealed marked increases in the total cell, lymphocyte and macrophage numbers.
Strain variation in Tv-induced HP was studied by using 4 kinds of syngeneic strains. C57Black/6 mice were high responders; C3H/He and Balb/C mice were low responders and CBA strain was intermediate.
Studies on the technique of BAL revealed that sufficient viable cells could be obtained by washing with 1ml saline 4 times. Histological examination of the lungs before and after the BAL procedure suggested that inflammatory and immune effector cells within the alveolar walls could be obtained by BAL.
Since lung pathology of athymic nude mice of high responders (C57Black/6N-nu) treated with Tv showed only minimal changes, there is a strong suggestion that the T cell-dependent immune system plays an essential role in the development of this murine HP model. We conclude that this murine model of HP is a useful tool for the study of the pathogenesis of human HP.