Effects of steroid treatment on immune defenses of the rat lung against Pneumocystis carinii
Abstract
The overall goal of this study was to characterize immune responsiveness of the lungs of steroid-treated rats against Pneumocystis carinii. Pneumocystis infection was induced in young rats by treatment with dexamethasone. Ultrastructural studies demonstrated that macrophages collected from rats following nine weeks of steroid treatment were capable of phagocytosis. Several aspects of phagocytic function were investigated in macrophages from rats following one and three weeks of steroid treatment. A yeast phagocytosis assay was first used to quantitate parameters of macrophage phagocytic function. This assay revealed that steroid treatment alone enhanced the phagocytic capabilities of macrophages. Treatment with immune modulating agents (opsonizing serum and muramyl dipeptide) further increased select parameters of phagocytosis. A similar assay was developed for P. carinii by measuring numbers of organisms associated with alveolar macrophages. Steroid treatment alone did not influence the association capacity of macrophages. Use of the immune modulating agents, specific opsonizing serum and muramyl dipeptide, selectively increased association of P. carinii with macrophages. The competency of the lung microenvironment is important in the pathogenesis of P. carinii infection. To examine this, acellular lung lavagates from steroid-treated rats were tested for their effects on in vitro growth of P. carinii on a rat lung cell line (L2). Acellular fluids, collected from the explanted lungs of steroid-treated rats, were similarily tested for their effects on P. carinii growth. Lung lavagates and lung culture fluids from three week steroid-treated rats enhanced Pneumocystis growth in vitro. In another approach to characterize lung defenses against P. carinii infection, certain biological agents were tested for their effects on Pneumocystis viability. Viable Pneumocystis were demonstrated by epifluorescent microscopy following staining with fluorescein diacetate. The substances tested (immune rat lung lavagates, tumor necrosis factor and various sera) were found to be deleterious to P. carinii viability.
Degree
Ph.D.
Advisors
Burnstein, Purdue University.
Subject Area
Veterinary services
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