THE GENERATION OF NITRIC-OXIDE PARTICIPATES IN GAMMA-IFN-INDUCED MHC CLASS-II ANTIGEN EXPRESSION BY CULTURED ASTROCYTOMA-CELLS

The effects of interferon gamma (gammaIFN) on the MHCII antigen expression by human cultured astrocytoma cells were investigated. the co-incubation of gammaIFN 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 gammaIFN-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 gammaIFN. Furthermore, gammaIFN 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 gammaIFN 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.