Growth characteristics and pathogenesis of experimental Pneumocystis carinii pneumonia

Abstract

Pneumocystis carinii pneumonia was produced in two groups of rats by the administration of corticosteroids, a low-protein (8%) diet, and tetracycline in the drinking water. A third group not on corticosteroids or a low-protein diet served as controls. Members of the first group were sacrificed weekly for 8 weeks, and lungs were examined. A highly significant correlation was found between the histopathological assessment of the intensity of P. carinii infection and the number of cysts counted in enzyme-digested lungs. P. carinii progressively filled alveoli, and cyst counts increased from -104 to 109 cysts/g of lung at peak intensity of infection at 7 to 8 weeks. The second group of rats was placed on a regular diet and tapering doses of corticosteroids after week 4, and they were sacrificed at varying intervals for up to 21 weeks. P. carinii was not cleared from the lungs until after week 13 (more than 6 weeks after discontinuation of all steroids). Histologically, there was an increased prominence of alveolar macrophages and the progressive development of interstitial mononuclear cell infiltrate and fibrosis. Thus, P. carinii grows slowly in vivo and interacts with specific host cells. The resulting changes may be important in the pathogenesis of the infection and in the clearance of the organism from the lung after immunocompetence has been restored.

Outbreaks of Pneumocystis carinii pneumonia in colonies of immunodeficient mice

“…On histopathologic examination, the alveoli showed the typical foamy eosinophilic material, but the host inflammatory response was mild and nonspecific. These features are similar to those found in previous studies of P. carinii pneumonia in nude mice and in corticosteroid-treated normal mice and rats (37,38,43).…”

Collagenases and the serine proteinases elastase and cathepsin G in steroid-induced Pneumocystis carinii pneumonia

“…There are fundamental problems with the animal model in separating the cellular and biochemical observations associated with the immunosuppression from those associated with PCP (because all of the immunosuppressed animals developed PCP) and in identifying the activities associated with P. carinii from those associated with the lung parenchyma and the cells of the immune system. In spite of these limitations, it was found that the experimental PCP described here was histopathologically similar to the classical textbook description; namely, it was characterized by an increased width of alveolar septa, the existence of perialveolar and diffuse fibroses, and the presence of intra-alveolar eosinophilic material and an exudate containing macrophages and interstitial mononuclear cell infiltrates (8,41). Ultrastructurally, type I epithelial cells showed signs of degeneration and the formation of subepithelial blebs between the type I cells and the basal lamina.…”

“…It is characterized clinically by dyspnea, tachypnea, and hypoxemia (5,11,12). The lung tissue is usually diffusely involved, with the alveoli becoming filled with a foamy, proteinaceous material (41). This foamy debris effectively diminishes the alveolar surface area available for gas exchange and therefore causes shunting of unoxygenized blood with a resultant disturbed ventilation-perfusion ratio and hypoxemia (21).…”

Comparison of histological and immunological techniques for detection of Pneumocystis carinii in rat bronchial lavage fluid

“…On the other hand, Giemsa stains a variety of host cells, sometimes making it difficult to distinguish P. carinii; the small size of trophozoites and their tendency to clump have precluded accurate quantitation of this form of the organism. We and others have found that counting the number of cysts by the use of cell wall stains provides the most reliable marker of the number of Pneumocystis organisms (28,39,40).…”