ACTION OF CHLOROQUINE ON NITRIC-OXIDE PRODUCTION AND PARASITE KILLINGBY MACROPHAGES

Chloroquine is known to inhibit several functions of macrophages, but its effect on the nitric oxide (NO)-dependent parasite killing capacit y of macrophages has not been documented. NO synthesis by interferon-g amma-induced mouse and casein-elicited rat macrophages was significant ly and irreversibly inhibited by chloroquine. The activity of the indu cible NO synthase was not directly altered, but previous incubation of macrophages with chloroquine decreased it. Chloroquine did not alter arginase activity or arginine uptake. NADPH diaphorase activity, an in dicator of NO synthase was impaired. Western blotting showed that indu cible NO synthase synthesis was blocked by chloroquine. The blocking o f NO formation by chloroquine resulted in increased infection of mouse peritoneal macrophages by Trypanosoma cruzi (T. cruzi). This suggests that chloroquine decreases NO formation by macrophages by inhibiting the induction of NO synthase. The findings are further evidence that N O is involved in the anti-parasitic response of macrophages. (C) 1998 Elsevier Science B.V. All rights reserved.