Neuromyelitis optica IgG and natural killer cells produce NMO lesions in mice without myelin loss
العنوان: | Neuromyelitis optica IgG and natural killer cells produce NMO lesions in mice without myelin loss |
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المؤلفون: | Marios C. Papadopoulos, Samira Saadoun, Hua Zhang, Alan S. Verkman, Jeffrey Bennett, Julien Ratelade |
المصدر: | Acta Neuropathologica. 123:861-872 |
بيانات النشر: | Springer Science and Business Media LLC, 2012. |
سنة النشر: | 2012 |
مصطلحات موضوعية: | Pathology, medicine.medical_specialty, Article, Immunoglobulin G, Pathology and Forensic Medicine, Natural killer cell, Lesion, Mice, Cellular and Molecular Neuroscience, medicine, Animals, Humans, Cells, Cultured, Myelin Sheath, Aquaporin 4, Mice, Knockout, Antibody-dependent cell-mediated cytotoxicity, Neuromyelitis optica, biology, Neuromyelitis Optica, Antibody-Dependent Cell Cytotoxicity, Antibodies, Monoclonal, Complement System Proteins, medicine.disease, Killer Cells, Natural, Disease Models, Animal, medicine.anatomical_structure, Spinal Cord, Astrocytes, Immunology, Monoclonal, biology.protein, Neurology (clinical), medicine.symptom, Astrocyte |
الوصف: | 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. |
وصف الملف: | application/pdf |
تدمد: | 1432-0533 0001-6322 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0d247f62ae9e383acae8b64b502dc8c3 https://doi.org/10.1007/s00401-012-0986-4 |
حقوق: | OPEN |
رقم الأكسشن: | edsair.doi.dedup.....0d247f62ae9e383acae8b64b502dc8c3 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 14320533 00016322 |
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