Macrophage colony-stimulating factor induction of enhanced macrophage anticryptococcal activity: synergy with fluconazole for killing.
Enhancement of anticryptococcal activity in macrophages by macrophage colony-stimulating factor (M-CSF) and possible synergy between macrophages and fluconazole for killing of Cryptococcus neoformans were tested. M-CSF (48 h)-treated macrophages underwent dramatic morphologic changes and inhibited cryptococcal multiplication by 96% +/- 4%, which was greater (P < .001) than that of macrophages cultured in medium alone. M-CSF (5000 units/mL) induced optimal anticryptococcal activity but did not increase percentage of phagocytosis. NG-mono-methyl-L-arginine did not affect enhanced fungistatic activity. For a very fluconazole-sensitive isolate, fungistatic macrophages synergized with fungistatic doses of fluconazole for killing; for a less sensitive isolate, synergy was significant only when macrophages were activated with M-CSF or interferon-gamma plus lipopolysaccharide; for a fluconazole-resistant isolate, macrophages collaborated with fluconazole for additive fungistasis but not killing, and M-CSF-treated macrophages were significantly more fungistatic with fluconazole than were nonactivated macrophages.
Brummer
E
E
Dept. of Medicine, Santa Clara Valley Medical Center, San Jose, CA 95128-2699.
Stevens
D A
DA
D000818:Animals; D002478:Cells, Cultured; D003455:Cryptococcus neoformans / Q000187:drug effects / Q000276:immunology*; D015725:Fluconazole / Q000494:pharmacology*; D005856:Germ-Free Life; D007700:Kinetics; D008262:Macrophage Activation; D016173:Macrophage Colony-Stimulating Factor / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010587:Phagocytosis
D016173:Macrophage Colony-Stimulating Factor; D015725:Fluconazole