Anti-MHV3 state induced by IFN gamma in macrophages is not related to arginine metabolism.
In contrast to BALB/c mouse macrophages, the A/J macrophages after activation by interferon gamma (IFN gamma) develop an anti-MHV3 effect which correlates with the resistance to virus infection. To understand the cellular basis of this antiviral effect, we studied the possible involvement of arginine metabolism through nitric oxide (NO) and arginase induction, since these metabolic pathways have been described as implicated in antiviral activities of macrophages. The studies were performed by activating macrophages with inducers of NO (IFN gamma) and arginase (IL4 IL10). NO synthase (iNOS) and arginase inhibitors (N-methyl-arginine, NMA, and hydroxyarginine, OH-ARG) were used. The results show that in both macrophage populations, no spontaneous synthesis of NO occurred and the MHV3 enhanced the NO release induced by IFN gamma. After activation with IFN gamma, BALB/c macrophages released higher amounts of NO than the A/J macrophages. The inhibition of IFN gamma-induced NO-synthesis with NMA or with arginine free medium did not affect the virus replication. In BALB/c macrophages, IL4 or IL10, induced higher amounts of arginase than in A/J macrophages. In both macrophage populations the MHV3 infection had no influence on the arginase synthesized, and the inhibition of the arginase with OH-ARG had no influence on the virus growth. The level of MHV3 replication or inhibition was also not influenced when we used macrophages from knockout mice for the iNOS gene, and as a consequence were unable of synthesizing NO. These data indicate that NO and arginase do not participate in the anti-MHV3 state induced by IFN gamma in macrophages.
Pereira
C A
CA
Instituto Butantan, Laboratorio de Imunologia Viral, Sao Paulo, Brazil.
Soler
G
G
Modolell
M
M
D000818:Animals; D001119:Arginase / Q000378:metabolism; D001120:Arginine / Q000378:metabolism*; D002478:Cells, Cultured; D018352:Coronavirus Infections / Q000276:immunology; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000494:pharmacology*; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000821:virology*; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D006517:Murine hepatitis virus / Q000276:immunology* / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
D009569:Nitric Oxide; D007371:Interferon-gamma; D001120:Arginine; D019001:Nitric Oxide Synthase; D001119:Arginase