The generation of nitric oxide participates in gamma IFN-induced MHC class II antigen expression by cultured astrocytoma cells.
The effects of interferon gamma (gamma IFN) on the MHCII antigen expression by human cultured astrocytoma cells were investigated. The co-incubation of gamma IFN with T67 astrocytoma cells produced a dose-dependent increase of MHCII antigen expression as evaluated by flow cytometric (FACS) analysis and confocal laser microscopy analysis. The number of MHCII molecules expressed by gamma IFN-pretreated astrocytoma cells was reduced by co-incubation with N omega-nitro-L-arginine methyl ester (L-NAME), a selective inhibitor of the nitric oxide (NO)-synthesizing enzyme. In addition, methylene blue, which inhibits the biological activity of NO acting at the guanylate cyclase level, strongly antagonized the MHCII antigen expression on astrocytoma cells induced by gamma IFN. Furthermore, gamma IFN increased the activity of the inducible isoform of NO-synthase as well as the concentration of nitrite, one of the breakdown products of NO and the antiplatelet activity of astrocytoma cells. In conclusion, the present data show that gamma IFN increases the synthesis and release of NO by cultured astrocytoma cells and this could co-participate in the MHCII antigen expression by this cell type. Therefore, the generation of NO by cultured astrocytoma cells may represent an important step in the development of the immunocompetent activity of astrocytes.
Colasanti
M
M
Department of Biology, III University of Rome, Italy.
Mollace
V
V
Cundari
E
E
Massoud
R
R
Nisticò
G
G
Lauro
G M
GM
D000594:Amino Acid Oxidoreductases / Q000378:metabolism; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001254:Astrocytoma / Q000276:immunology* / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D008751:Methylene Blue / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase; D010974:Platelet Aggregation / Q000187:drug effects; D014407:Tumor Cells, Cultured
D000949:Histocompatibility Antigens Class II; D009569:Nitric Oxide; D007371:Interferon-gamma; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester