PNEUMOCYSTIS CARINII-INDUCED ACTIVATION OF THE RESPIRATORY BURST IN HUMAN MONOCYTES AND MACROPHAGES

Human monocytes and monocyte-derived macrophages were studied for thei r ability to phagocytose Pneumocystis carinii and produce superoxide ( O-2(-)) during the process. One x 10(6) freshly isolated monocytes, in cubated with 0.1-3.75 x 10(6) P. carinii cysts, increased O-2(-) produ ction in a dose-related way. Antibodies were essential for the process since opsonized, but not unopsonized, pneumocysts induced O-2(-) prod uction significantly above the response obtained by lung tissue from r ats (10.7 and 4.9 versus 3.0 fmol/cell per 90 min). The difference bet ween pneumocysts opsonized in untreated versus complement-depleted ser um was not significant (10.7 versus 12.6 fmol/cell per 90 min). Monocy te-derived macrophages also activated the respiratory burst when stimu lated with pneumocysts, and this effect could be significantly increas ed, from 4.2 to 8.8 fmol/cell per 90 min, when cells were primed with interferon-gamma (IFN-gamma). Cells primed with IL-3 also increased O- 2(-) production, though to a lesser extent. In contrast, granulocyte-m acrophage colony-stimulating factor (GM-CSF) had only a small effect o n the respiratory burst in cells stimulated with P. carinii. Priming w ith IFN-gamma increased the rate of phagocytosis in macrophages. After incubation for 90 min or more, however, the percentage of cells with phagocytic vacuoles was only slightly higher in IFN-gamma-primed cells . When examined by electron microscopy (EM), most vacuoles contained p artially or totally degraded pneumocysts. In conclusion, we have demon strated the ability of monocytes and monocyte-derived macrophages to i ngest and degrade pneumocysts, activating the respiratory burst during the process.