Experimental production of pulmonary granulomas. I. Immune granulomas induced by chemically modified cell walls and their constituents.

The intrabronchial instillation of stimulants in an oily vehicle induces a solitary inflammatory focus in the rabbit lung. When heat-killed tubercle bacilli were administered to tuberculo-immune animals, a necrotizing focus with cavities was induced. Delipidation of the bacterial cells stimulated the production of a necrotizing focus. In contrast, acetylation of the mycobacterial cell walls resulted in the replacement of cavity formation with epithelioid-cell granuloma production similar to that seen after the administration of Wax D, a peptidoglycolipid fraction of the cell walls. These lesions were induced much faster than in controls, indicating that some immune mechanisms are involved. In the present study of the specific granuloma induction mechanism, the biological activities of the chemical constituents of Wax D were examined. It was concluded that specific granuloma induction is due to the long delayed hypersensitivity antigenicity of Wax D which is brought about by the conjugation of biologically inactive mycolic acid with Arthus-antigenic peptidoglycan. Wax D glycolipids with delayed-type antigenicity also take part in the induction. The intrinsic adjuvant activity of these compounds may stimulate granuloma production. The haemagglutination antigenicity and Arthus-type antigenicity of the polysaccharide or peptidoglycan moiety are not involved.