Candidacidal mechanisms of peritoneal macrophages activated with lymphokines or gamma-interferon.
The mechanisms by which resident peritoneal macrophages, activated in vitro by lymphokines (LK) or recombinant gamma-interferon (IFN), kill Candida parapsilosis or C. albicans were studied. Resident non-activated peritoneal macrophages killed C. parapsilosis (55.5% SD 6.8%), but not C. albicans. This killing was completely inhibited by superoxide dismutase (SOD), partially by dimethyl sulphoxide (DMSO), but not by catalase or azide. Killing correlated with a brisk lucigenin-dependent chemiluminescence (CL) response by macrophages interacting with C. parapsilosis. No enhanced luminol-dependent CL response was observed in this system. This suggests that C. parapsilosis is killed by resident macrophages via a mechanism dependent on the presence of superoxide anion. By contrast, killing of C. parapsilosis by activated macrophages (49.0% SD 5.9%) was not inhibited by SOD or DMSO, suggesting the induction of a non-oxidative candidacidal mechanism. C. albicans was killed only by macrophages activated with IFN (52.0% SD 3.7%) or LK (55.7% SD 2.8%). Inhibition of killing by SOD was greater in IFN- than in LK-activated macrophages. Conversely, killing by LK-, but not IFN-, activated macrophages was significantly inhibited by catalase, DMSO or azide. The killing by LK-activated macrophages, and its inhibition by scavengers, correlated with the luminol-dependent CL response. The non-killing resident macrophages interacting with C. albicans made lucigenin-dependent CL responses similar to those of activated macrophages. The mechanisms enabling killing of C. albicans induced by activation appear to be different for LK and IFN, and appear to depend upon the myeloperoxidase systems and superoxide respectively.
Brummer
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Department of Medicine, Santa Clara Valley Medical Center, San Jose, CA 95128.
Stevens
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DA
D000166:Acridines / Q000494:pharmacology; D000818:Animals; D002175:Candida / Q000276:immunology*; D002176:Candida albicans / Q000276:immunology; D002374:Catalase / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D008163:Luminescent Measurements; D008165:Luminol / Q000494:pharmacology; D008222:Lymphokines / Q000494:pharmacology*; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010537:Peritoneum / Q000166:cytology; D010587:Phagocytosis; D013482:Superoxide Dismutase / Q000494:pharmacology
D000166:Acridines; D008222:Lymphokines; C033472:10,10'-dimethyl-9,9'-biacridinium; D008165:Luminol; D007371:Interferon-gamma; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D004121:Dimethyl Sulfoxide