Nitric oxide-mediated cytostatic activity on Trypanosoma brucei gambiense and Trypanosoma brucei brucei.
Macrophages collected from BCG-infected mice or exposed in vitro to interferon-gamma plus lipopolysaccharide developed a cytostatic activity on Trypanosoma brucei gambiense and Trypanosoma brucei brucei. This trypanostatic activity of activated macrophages was inhibited by addition of N-monomethyl-L-arginine, an inhibitor of the L-arginine-nitric oxide (NO) metabolic pathway, indicating a role for NO as the effector molecule. Contrary to trypanosomes treated with N2gas, trypanosomes treated with NO gas did not proliferate in vitro on normal macrophages. Compared to mice infected with control parasites, mice infected with NO-treated parasites had decreased parasitemias in the first days postinfection and had a prolonged survival. Addition of excess iron reversed the trypanostatic effect of both activated macrophages and NO gas. These data show that activated macrophages exert an antimicrobial effect on T.b. gambiense and T.b. brucei through the L-arginine-NO metabolic pathway. In trypanosomes, NO could trigger iron loss from critical targets involved in parasite division. The participation of this effector mechanism among the other immune elements involved in the control of African trypanosomes (antibodies, complement, phagocytic events) remains to be defined.
Vincendeau
P
P
Laboratoire de Parasitologie, Université de Bordeaux II, France.
Daulouède
S
S
Veyret
B
B
Darde
M L
ML
Bouteille
B
B
Lemesre
J L
JL
D000818:Animals; D003602:Cytotoxicity, Immunologic; D005260:Female; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009163:Mycobacterium bovis / Q000276:immunology; D009569:Nitric Oxide / Q000494:pharmacology*; D014346:Trypanosoma brucei brucei / Q000187:drug effects* / Q000254:growth & development / Q000276:immunology; D014347:Trypanosoma brucei gambiense / Q000187:drug effects* / Q000254:growth & development / Q000276:immunology
D008070:Lipopolysaccharides; D009569:Nitric Oxide; D007371:Interferon-gamma