Resistance and susceptibility to Marek's disease: nitric oxide synthase/arginase activity balance.
The metabolic NO pathway, catalyzed by the enzyme NO synthase in macrophages, is a key defense element against viruses and tumors. However, arginase is an other enzyme able to metabolize the substrate L-arginine, and the two enzymes are alternatively regulated by Th1 and Th2 cytokines in murine macrophages. Marek's disease is characterized by strong immunosuppression and development of T-cell lymphomas in chickens. Inoculation of the very virulent strain of MDV RB-1B induced strong and long-lasting arginase macrophage-dependent activity, which was inhibited by L-norvaline in vitro, but induced low NO production in monocytes and splenocytes from highly susceptible B(13)/B(13) chickens. By contrast, in B(21)/B(21) chickens genetically resistant to tumor development, RB-1B induced a weak and transient increase in arginase activity and strong NO production. The vaccinal HVT strain did not induce any arginase activity in monocytes or splenocytes. Moreover, vaccination with HVT prevented tumor appearance after RB-1B challenge and increase in arginase activity, but favored NO production in susceptible chickens. Differential expression of NO synthase and arginase was modulated in chicken macrophages, with IFN-gamma and LPS being strong inducers of both, depending on the type of macrophage, and TGF-beta 1 and PGE(2) stimulating only arginase activity. This increase in arginase activity in macrophages from chickens inoculated with Marek's disease virus might thus be due to a direct effect of the virus on macrophages, possibly through viral products, or to indirect effects on the cytokine balance.
Djeraba
Aouatef
A
Institut National de la Recherche Agronomique, Station de Pathologie Aviaire et de Parasitologie, 37380 Nouzilly, France.
Musset
Eugène
E
van Rooijen
Nico
N
Quéré
Pascale
P
D000818:Animals; D001119:Arginase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002460:Cell Line; D002645:Chickens / Q000235:genetics; D004198:Disease Susceptibility / Q000662:veterinary; D008264:Macrophages / Q000201:enzymology; D025922:Mardivirus / Q000276:immunology / Q000472:pathogenicity; D008380:Marek Disease / Q000201:enzymology* / Q000276:immunology / Q000821:virology; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D011201:Poultry Diseases / Q000201:enzymology* / Q000276:immunology / Q000821:virology; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D014611:Vaccination / Q000662:veterinary; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology
D009569:Nitric Oxide; C005313:norvaline; D019001:Nitric Oxide Synthase; D001119:Arginase; D014633:Valine