Pneumocystis carinii-induced activation of the respiratory burst in human monocytes and macrophages

Abstract

SUMMARY Human monocytes and monocyte-derived macrophages were studied for their ability to phagocytose Pneumocystis carinii and produce superoxide (O−2) during the process. One × 106 freshly isolated monocytes. incubated with 0.1 – 3.75 × 106P. carinii cysts, increased O−2 production in a dose-related way. Antibodies were essential for the process since opsonized, but not unopsonized, pneumocysts induced O−2 production significantly above the response obtained by lung tissue from rats (10.7 and 4.9 versus 30 fmol/cell per 90 min). The difference between pneumocysts opsonized in untreated versus complement-depleted serum was not significant (10.7 versus 12.6 fmol/cell per 90 min). Monocyte-derived macrophages also activated the respiratory burst when stimulated with pneumocysts, and this effect could be significantly increased, from 4.2 to 8.8 fmol/cell per 90 min, when cells were primed with interferon-gamma (IEN-γ). Cells primed with IL-3 also increased O2 production, though to a lesser extent. In contrast, granulocyte-macrophage colony-stimulating factor (GM-CSF) had only a small effect on the respiratory burst in cells stimulated with P. carinii. Priming with IEN-γ 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-γ-primed cells. When examined by electron microscopy (EM), most vacuoles contained partially or totally degraded pneumocysts. In conclusion, we have demonstrated the ability of monocytes and monocyte-derived macrophages to ingest and degrade pneumocysts. activating the respiratory burst during the process.