Microglial cell cytotoxicity of oligodendrocytes is mediated through nitric oxide

• Published in: The Journal of immunology (1950) Vol. 151; no. 4; pp. 2132 - 2141
• Main Authors: Merrill, JE, Ignarro, LJ, Sherman, MP, Melinek, J, Lane, TE
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Assoc Immnol 15.08.1993; American Association of Immunologists
• Subjects: Ageing, cell death; Animals; Biological and medical sciences; Cell Adhesion Molecules - metabolism; Cell Death; Cell physiology; Cells, Cultured; Fundamental and applied biological sciences. Psychology; In Vitro Techniques; Intercellular Adhesion Molecule-1; Lymphocyte Function-Associated Antigen-1 - metabolism; Molecular and cellular biology; Neuroglia - cytology; Neuroglia - immunology; Nitric Oxide - metabolism; Oligodendroglia - immunology; Rats; Transforming Growth Factor beta - pharmacology; Tumor Necrosis Factor-alpha - physiology; Cell function; Rat; Rodentia; Cytotoxicity; Mechanism; Microglia; Vertebrata; Mammalia; Oligodendrocyte; Cell population; Cell death; Nitrogen monoxide; Brain (vertebrata)
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.151.4.2132

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.