Microglial cell cytotoxicity of oligodendrocytes is mediated through nitric oxide.

作者: Thomas E. Lane , Jean E. Merrill , Louis J. Ignarro , Michael P. Sherman , Judy Melinek

DOI:

关键词: BiochemistryNitric oxideCell biologyIn vitroBiologyOligodendrocyteProgrammed cell deathMicrogliaAntibodyIntracellularCytotoxicity

摘要: 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 antibodies TNF-alpha, intercellular adhesion molecule-1 (ICAM-1), and leukocyte functional Ag-1. Ameboid microglial cells spontaneously produce detectable levels the NO metabolite nitrite (NO2-). Stimuli such PMA, LPS, and/or IFN-gamma induce micromolar concentrations NO2- within 24 h. TNF-alpha increases IFN gamma but not LPS-induced production. Incubation with target also production a contact-dependent manner. synthase antagonists, anti TNF-alpha. Neither antileukocyte Ag-1 nor anti-ICAM-1 inhibit presence or absence oligodendrocytes. Indeed, treatment There correlation between cell killing suggesting may be mechanism death oligodendrocyte possibly play role lesion formation multiple sclerosis.

参考文章(46)
H H Birdsall, C Lane, D C Anderson, M N Ramser, Induction of VCAM-1 and ICAM-1 on human neural cells and mechanisms of mononuclear leukocyte adherence. Journal of Immunology. ,vol. 148, pp. 2717- 2723 ,(1992)
M L Lohmann-Matthes, T Decker, B Luettig, Evidence for the existence of two forms of membrane tumor necrosis factor: an integral protein and a molecule attached to its receptor. Journal of Immunology. ,vol. 143, pp. 4034- 4038 ,(1989)
D Hinton, J E Merrill, F M Hofman, R I von Hanwehr, S B Mizel, C A Dinarello, Immunoregulatory molecules and IL 2 receptors identified in multiple sclerosis brain. Journal of Immunology. ,vol. 136, pp. 3239- 3245 ,(1986)
C A Nacy, J T Hockmeyer, M S Meltzer, R M Crawford, S J Green, Leishmania major amastigotes initiate the L-arginine-dependent killing mechanism in IFN-gamma-stimulated macrophages by induction of tumor necrosis factor-alpha. Journal of Immunology. ,vol. 145, pp. 4290- 4297 ,(1990)
Robert Rothlein, Charles A. Dinarello, Atul K. Bhan, Michael L. Dustin, Timothy A. Springer, Induction by IL 1 and interferon-gamma: tissue distribution, biochemistry, and function of a natural adherence molecule (ICAM-1). Journal of Immunology. ,vol. 137, pp. 245- 254 ,(1986)
James W. Larrick, Susan C. Wright, Cytotoxic mechanism of tumor necrosis factor‐α The FASEB Journal. ,vol. 4, pp. 3215- 3223 ,(1990) , 10.1096/FASEBJ.4.14.2172061
G Kantwerk-Funke, H Kolb, V Burkart, V Kolb-Bachofen, B Appels, J Funda, Spontaneous cytotoxicity of macrophages against pancreatic islet cells. Journal of Immunology. ,vol. 142, pp. 3803- 3808 ,(1989)
D Giulian, TJ Baker, Characterization of ameboid microglia isolated from developing mammalian brain The Journal of Neuroscience. ,vol. 6, pp. 2163- 2178 ,(1986) , 10.1523/JNEUROSCI.06-08-02163.1986
A A Brian, P Kuhlman, V T Moy, B A Lollo, The accessory function of murine intercellular adhesion molecule-1 in T lymphocyte activation. Contributions of adhesion and co-activation. Journal of Immunology. ,vol. 146, pp. 1773- 1782 ,(1991)