The role of cathepsin D in the pathogenesis of tuberculosis. A histochemical study employing unlabeled antibodies and the peroxidase antiperoxidase complex

Cathepsin D was visualized in free pulmonary alveolar macrophages (AM), in oil induced peritoneal macrophages (MN) and in rabbit pulmonary and dermal BCG lesions with unlabeled antibodies and the peroxidase antiperoxidase (PAP) complex. Large amounts of cathepsin D were present in AM and lower amounts in MN. In the lung this enzyme was richest in the alveolar macrophages that accumulated around the BCG lesions. In the dermal lesions, cathepsin D was in highest concentration in macrophages at the border of the necrotic (liquefying) centers. It was also found in high concentration in keratinizing cells of the dermal epithelium and hair follicles. It did not, however, increase appreciably in many of the activated macrophages that stained intensely for the lysosomal enzyme β galactosidase. In fact, many epithelioid cells with high β galactosidase activity contained no visible cathepsin D. This proteinase does not, therefore, seem to be primarily involved in the lymphocyte mediated macrophage activation associated with acquired cellular resistance to tubercle bacilli. It is probably more involved with cell autolysis, with the digestion of ingested necrotic debris and, in all likelihood, with the process of liquefaction, the most adverse event in the pathogenesis of tuberculosis in man.