PT - JOURNAL ARTICLE AU - Merrill, J E AU - Ignarro, L J AU - Sherman, M P AU - Melinek, J AU - Lane, T E TI - Microglial cell cytotoxicity of oligodendrocytes is mediated through nitric oxide. DP - 1993 Aug 15 TA - The Journal of Immunology PG - 2132--2141 VI - 151 IP - 4 4099 - http://www.jimmunol.org/content/151/4/2132.short 4100 - http://www.jimmunol.org/content/151/4/2132.full SO - J. Immunol.1993 Aug 15; 151 AB - Rat ameboid microglia are able to lyse rat oligodendrocytes in vitro. The lysis is inhibited by transforming growth factor-beta, antagonists of nitric oxide (NO) production, as well as antibodies to TNF-alpha, intercellular adhesion molecule-1 (ICAM-1), and leukocyte functional Ag-1. Ameboid microglial cells spontaneously produce detectable levels of the NO metabolite nitrite (NO2-). Stimuli such as PMA, LPS, and/or IFN-gamma induce micromolar concentrations of NO2- within 24 h. TNF-alpha increases IFN gamma but not LPS-induced NO2- production. Incubation with target oligodendrocytes also increases NO2- production in a contact-dependent manner. NO2- production is inhibited by NO synthase antagonists, transforming growth factor-beta, and anti TNF-alpha. Neither antileukocyte functional Ag-1 nor anti-ICAM-1 inhibit NO2- production by microglia in the presence or absence of oligodendrocytes. Indeed, anti-ICAM-1 treatment increases NO2- production. There is a correlation between ameboid microglial cell killing of oligodendrocytes and NO2- production suggesting NO may be a mechanism of death of the oligodendrocyte and possibly play a role in lesion formation in multiple sclerosis.