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.