Relationship between granulocyte macrophage-colony stimulating factor, tumour necrosis factor-alpha and Trypanosoma cruzi infection of murine macrophages.
Gamma interferon (IFN-gamma)-activated macrophages control Trypanosoma cruzi infection via nitric oxide (NO), recently recognized as a major effector molecule. Granulocyte macrophage-colony stimulating factor (GM-CSF) is a multipotent cytokine secreted by macrophages and many other cells. It induces the production of tumour necrosis factor alpha (TNF-alpha), another cytokine also secreted by macrophages and involved in the control of T. cruzi infection. However, no data are available on the relationship between GM-CSF, TNF-alpha and NO produced by macrophages activated by IFN-gamma and infected with T. cruzi. To highlight this relationship, mouse peritoneal macrophages (MPM) and two c-myc retrovirus-induced macrophage cell lines (9.1.1 and BMM8), respectively characterized by a constitutive and an inducible production of GM-CSF, were activated with IFN-gamma and/or GM-CSF and infected with T. cruzi. Our results indicate that T. cruzi upregulates GM-CSF release from MPM and from the two macrophage cell lines, activated (or not) by IFN-gamma. A high autocrine production of GM-CSF or an exogenous supply of GM-CSF is correlated with an enhanced release of TNF-alpha and NO, inducing an improved control of T. cruzi infection by IFN-gamma-activated MPM.
Olivares Fontt
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E
Laboratoire d'Immunologie (CP 615), Faculté de Médecine, Université Libre de Bruxelles, Belgium.
Vray
B
B
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000378:metabolism* / Q000469:parasitology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D009573:Nitrites / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011994:Recombinant Proteins; D014349:Trypanosoma cruzi / Q000254:growth & development*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D015854:Up-Regulation; D019323:omega-N-Methylarginine
D009573:Nitrites; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D001120:Arginine; D006861:Hydrogen Peroxide