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Neuromyelitis Optica Immunoglobulin G present in sera from neuromyelitis optica patients affects aquaporin‐4 expression and water permeability of the astrocyte plasma membrane
Author(s) -
Melamud Luciana,
Fernández Juan M.,
Rivarola Valeria,
Di Giusto Gisela,
Ford Paula,
Villa Andrés,
Capurro Claudia
Publication year - 2012
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.22822
Subject(s) - neuromyelitis optica , aquaporin 4 , chemistry , antibody , aquaporin , polyclonal antibodies , autoantibody , astrocyte , immunofluorescence , water channel , immunoglobulin g , immunology , microbiology and biotechnology , central nervous system , biology , biochemistry , endocrinology , mechanical engineering , engineering , inlet
NMO‐IgG autoantibody selectively binds to aquaporin‐4 (AQP4), the most abundant water channel in the central nervous system and is now considered a useful serum biomarker of neuromyelitis optica (NMO). A series of clinical and pathological observations suggests that NMO‐IgG may play a central role in NMO physiopathology. The current study evaluated, in well‐differentiated astrocytes cultures, the consequences of NMO‐IgG binding on the expression pattern of AQP4 and on plasma membrane water permeability. To avoid or to facilitate AQP4 down‐regulation, cells were exposed to inactivated sera in two different situations (1 hr at 4°C or 12 hr at 37°C). AQP4 expression was detected by immunofluorescence studies using a polyclonal anti‐AQP4 or a human anti‐IgG antibody, and the water permeability coefficient was evaluated by a videomicroscopy technique. Our results showed that, at low temperatures, cell exposure to either control or NMO‐IgG sera does not affect either AQP4 expression or plasma membrane water permeability, indicating that the simple binding of NMO‐IgG does not affect the water channel's activity. However, at 37°C, long‐term exposure to NMO‐IgG induced a loss of human IgG signal from the plasma membrane along with M1‐AQP4 isoform removal and a significant reduction of water permeability. These results suggest that binding of NMO‐IgG to cell membranes expressing AQP4 is a specific mechanism that may account for at least part of the pathogenic process. © 2012 Wiley Priodicals, Inc.