Experimental granulomatous pneumonitis: immunologic, histologic, and ultrastructural correlations.

not significantly different from control animals suggesting that the total number of activated macrophages was small. Intratracheal inoculation with M faeni antigen resulted in the production of anti-M faeni precipitating antibodies in serum of all inoculated animals. Anti-M faeni precipitins demonstrated by counterimmunoelec-trophoresis were also found in 14 of 16 concentrated h g wash specimens at 14 days and in 15 of 16 animals at 21 days. Determination of immunoglobulins by single radial diffusion in bronchial lavage specimens of all control and M faeni inoculated animals revealed IgG and IgA to be present at 14 and 21 days. IgM was noted in only 6 of the 40 total specimens analyzed and when detected was present in low concentrations at both 14 and 21 days. Levels of IgG and IgA were 384 + 31 and 101 + 12 mg % respectively in normal controls. Immunized rabbits had sigdcantly increased I& and IgA levels (614 + 34 and 219 + mg % respectively). The conclusions that one may draw from this study are as follows: 1) intratracheal inoculation of rabbits with M faeni produces a reversible mononuclear inter-stitial pneumonitis similar to that seen in man; 2) this pneumonitis is associated with intraalveolar accumulation of macrophages with increased percentages of lymphocytes and granulocytes early in the course of the lesion; 3) associated with this proliferative cellular response is evidence of macrophage stimulation and MIF production by bronchoalveolar lymphocytes. These data, together with other studies demonstrating ability to produce the same pathologic lesions by passive transfer of sensitized lymphoid cells followed by respiratory tract ~hallenge,~ suggest that delayed (cell-mediated) hyper-sensitivity plays a role in the pathogenesis of these experimental lesions in rabbits; 4) in addition, the presence of precipitins and increased immunoglobulin levels in bronchial secretions suggest a role for humoral immune mechanisms in either disease pathogenesis or host defense against inhaled actinomycete antigen. The heterogeneous immune response noted in this study is consistent with current findings in hypersensitiv-ity pneumonitis in man7 and it is reasonable to postulate that both hurnoral and cellular hypersensitivity may play a role in the pathogenesis of this pulmonary disorder. 1 Reynolds HT, Thompson RE, Devlin HB: Development of cellular and humoral immunity in the respiratory tract of rabbits of Pseudomonas lipopolysaocharide. J Clin Invest 53: 1351, 1974 2 Bibedeld G: Macrophage migration inhibition in response to experimental mycoplasrna pneumonia infection in the hamster. A llergic diseases of the …