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Acta Neuropathologica

Erschienen in:

01.06.2012 | Original Paper

Neuromyelitis optica IgG and natural killer cells produce NMO lesions in mice without myelin loss

verfasst von: Julien Ratelade, Hua Zhang, Samira Saadoun, Jeffrey L. Bennett, Marios C. Papadopoulos, A. S. Verkman

Erschienen in: Acta Neuropathologica | Ausgabe 6/2012

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Abstract

The pathogenesis of neuromyelitis optica (NMO) involves targeting of NMO-immunoglobulin G (NMO-IgG) to aquaporin-4 (AQP4) on astrocytes in the central nervous system. Prior work provided evidence for complement-dependent cytotoxicity (CDC) in NMO lesion development. Here, we show that antibody-dependent cellular cytotoxicity (ADCC), in the absence of complement, can also produce NMO-like lesions. Antibody-dependent cellular cytotoxicity was produced in vitro by incubation of mouse astrocyte cultures with human recombinant monoclonal NMO-IgG and human natural killer cells (NK-cells). Injection of NMO-IgG and NK-cells in mouse brain caused loss of AQP4 and GFAP, two characteristic features of NMO lesions, but little myelin loss. Lesions were minimal or absent following injection of: (1) control (non-NMO) IgG with NK-cells; (2) NMO-IgG and NK-cells in AQP4-deficient mice; or (3) NMO-IgG and NK-cells in wild-type mice together with an excess of mutated NMO-IgG lacking ADCC effector function. NK-cells greatly exacerbated NMO lesions produced by NMO-IgG and complement in an ex vivo spinal cord slice model of NMO, causing marked myelin loss. NMO-IgG can thus produce astrocyte injury by ADCC in a complement-independent and dependent manner, suggesting the potential involvement of ADCC in NMO pathogenesis.

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Titel: Neuromyelitis optica IgG and natural killer cells produce NMO lesions in mice without myelin loss
verfasst von: Julien Ratelade
Hua Zhang
Samira Saadoun
Jeffrey L. Bennett
Marios C. Papadopoulos
A. S. Verkman
Publikationsdatum: 01.06.2012
Verlag: Springer-Verlag
Erschienen in: Acta Neuropathologica / Ausgabe 6/2012
Print ISSN: 0001-6322
Elektronische ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-012-0986-4

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