実験的肺空洞形成

抄録

Cavities in the lungs are most commonly seen in the chronic type of human tuberculosis and still provide a difficult problem in the treatment of tuberculosis. However, most of the studies on experimental tuberculosis were concerned with acute and disseminated tuberculosis. The pathogenesis of the cavity formation was poorly understood, because of the difficulties in producing cavities in animal lungs. In the course of the studies, cavity formation has been observed by some investigators. Wells, Lurie and Ratcliffe reported that the rabbits that had received presensitization or preinfection with tubercle bacilli sometimes produced pulmonary cavities after an aerogenic infection with virulent tubercle bacilli. Steenken, Yesner and coworkers reported that thin-wall bullous cavities frequently appeared early in the course of effective chemotherapy in rabbits infected by inhalation with virulent bacilli.
Yamamura and coworkers presented a simple and reliable method to produce cavities in the lungs of animals and attempts have been made with this technique to clarify the pathogenesis of cavity formation in tuberculosis. In these studies, cavities were produced not only by live tubercle bacilli, but also by heat-killed bacilli, and previous sensitization enhanced the probability of cavity formation. Administration of immunosuppressive agents such as 6-mercaptopu-rine, azathioprine, cortisone, and antilymphocyte serum to animals suppressed cavity formation in their lungs. Repeated injections with Tuberculin Active Peptide also prevented cavity formation in rabbits. These results suggest that the hypersensitivity of tuberculosis may play an important role in cavity formation. The active antigenic component responsible for cavity formation is socalled a lipoprotein (LP) isolated from tubercle bacilli by the method of Folch and Lees. A single intrapulmonary injection of the LP produced the cavity in nonsensitized animals, whereas no cavity resulted from the injection of the protein from the culture filtrate of tube rcle bacilli. However, the protein could produce a cavity in animals previously sensitized with tubercle bacilli. These findings indicate that the LP can act both as a sensitizing and as an eliciting agent, whereas the protein alone can act only as an eliciting agent.
Maeda and coworkers separated the LP into lipid and protein fractions by Sephadex LH -20 column chromatography. Neither lipid nor protein fraction alone had cavity -forming activity; however, restoration of the activity was observed by recombining both the fractions. The cavityforming activity was also reconstructed by combining the protein fraction with BCG -cell walls or cord factor, while no activity was recovered by the combination of the protein and other lipids such as phosphatide and acetylated wax D. The cell walls were used for potentiating the antigenicity of the protein as an adjuvant. The cell walls and cord factor alone also had no activity and only produced granulomatous lesions in the lungs. From these results, it would appear that in the process of the cavity formation, the antigenicity of the protein is enhanced by the adjuvancy of the lipids. After completion of the sensitization, the protein acts as the eliciting agent and causes the reaction followed by cavity formation. On the other hand, polysaccharide of mycobacteria seems to have no relation to cavity formation.