Action of chloroquine on nitric oxide production and parasite killing by macrophages.
Chloroquine is known to inhibit several functions of macrophages, but its effect on the nitric oxide (NO)-dependent parasite killing capacity of macrophages has not been documented. NO synthesis by interferon-gamma-induced mouse and casein-elicited rat macrophages was significantly and irreversibly inhibited by chloroquine. The activity of the inducible 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 indicator of NO synthase was impaired. Western blotting showed that inducible NO synthase synthesis was blocked by chloroquine. The blocking of 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 NO is involved in the anti-parasitic response of macrophages.
Hrabák
A
A
Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University of Medicine, Budapest, Hungary. hrabak@puskin.sote.hu
Sefrioui
H
H
Vercruysse
V
V
Temesi
A
A
Bajor
T
T
Vray
B
B
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D001119:Arginase / Q000378:metabolism; D001120:Arginine / Q000493:pharmacokinetics / Q000633:toxicity; D015153:Blotting, Western; D002364:Caseins / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D002738:Chloroquine / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009252:NADPH Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017208:Rats, Wistar; D014349:Trypanosoma cruzi
D000962:Antimalarials; D002364:Caseins; D002614:Chelating Agents; D009569:Nitric Oxide; D007371:Interferon-gamma; D002738:Chloroquine; D001120:Arginine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C496318:Nos2 protein, rat; D009252:NADPH Dehydrogenase; D001119:Arginase