期刊
JOURNAL OF NEUROIMMUNOLOGY
卷 215, 期 1-2, 页码 31-35出版社
ELSEVIER
DOI: 10.1016/j.jneuroim.2009.07.014
关键词
Neuromyelitis optica; Neuromyelitis optica antibody (NMO-IgG); Aquaporin-4; Multiple sclerosis; Apoptosis; Cell death
资金
- Fondo de Investigacions Sanitarias, Madrid, Spain [PI060070]
- Instituto de Salud Carlos [RD07/ 0060/0012]
NMO-IgG is a disease-specific autoantibody for neuromyelitis optica (NMO) that binds selectively to aquaporin-4 (AQ4). an astrocytic water channel. The normal distribution of AQP4 coincides with the sites of immunoglobulin and complement deposits in lesions found in autopsy studies. The underlying mechanisms of cytotoxicity by NMO-IgG on astrocytes are not well known. In this study we show that serum samples from seropositive NMO patients (21) induce a higher rate of cell death compared with sera from seronegative NMO (16), relapsing-remitting MS (20) patients, and healthy controls (24) on primary cultures of astrocytes. Similar results were obtained by two different techniques: lactate dehydrogenase release and tetrazolium-based viability assay. Cell death was only observed in the presence of active complement. The complement-dependent cytotoxicity was not accompanied by caspase-3/7 activation or increase in the percentage of apoptotic cells. Our data show that NMO-IgG induces a complement-dependent cytotoxicity of astrocytes in vitro, and suggest that a mechanism of cellular death by necrosis might be implicated in the pathophysiology of NMO. (C) 2009 Elsevier B.V. All rights reserved.
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