Pneumocystis carinii-induced activation of the respiratory burst in human monocytes and macrophages.
Human monocytes and monocyte-derived macrophages were studied for their ability to phagocytose Pneumocystis carinii and produce superoxide (O2-) during the process. One x 10(6) freshly isolated monocytes, incubated with 0.1-3.75 x 10(6) P. carinii cysts, increased O2- production in a dose-related way. Antibodies were essential for the process since opsonized, but not unopsonized, pneumocysts induced O2- production significantly above the response obtained by lung tissue from rats (10.7 and 4.9 versus 3.0 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 (IFN-gamma). 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 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 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.
Department of Medicine and Infectious Diseases, Marselisborg Hospital, Aarhus C, Denmark.
A L
AL
Laursen
B
B
Møller
J
J
Rungby
C M
CM
Petersen
P L
PL
Andersen
D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D008297:Male; D009000:Monocytes / Q000276:immunology* / Q000382:microbiology; D009895:Opsonin Proteins / Q000276:immunology; D011010:Pneumocystis / Q000276:immunology*; D016720:Pneumocystis Infections / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D016897:Respiratory Burst / Q000276:immunology*; D013481:Superoxides / Q000378:metabolism
D009895:Opsonin Proteins; D013481:Superoxides