title: Neuromyelitis Optica Immunoglobulin G present in sera from neuromyelitis optica patients affects aquaporin-4 expression and water permeability of the astrocyte plasma membrane.
abstract: 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.
authors.affiliation: Laboratorio de Biomembranas, Departamento de Fisiología y Biofísica, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Luciana
authors.initials: L
authors.lastname: Melamud
authors.forename: Juan M
authors.initials: JM
authors.lastname: Fernández
authors.forename: Valeria
authors.initials: V
authors.lastname: Rivarola
authors.forename: Gisela
authors.initials: G
authors.lastname: Di Giusto
authors.forename: Paula
authors.initials: P
authors.lastname: Ford
authors.forename: Andrés
authors.initials: A
authors.lastname: Villa
authors.forename: Claudia
authors.initials: C
authors.lastname: Capurro
mesh_terms: D000328:Adult; D000818:Animals; D000831:Animals, Newborn; D000951:Antigens, Neoplasm / Q000378:metabolism; D051401:Aquaporin 4 / Q000378:metabolism*; D001253:Astrocytes / Q000187:drug effects* / Q000502:physiology; D019921:Biotinylation; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D009471:Neuromyelitis Optica / Q000276:immunology* / Q000473:pathology; D010539:Permeability / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D051381:Rats; D014867:Water / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000951:Antigens, Neoplasm; D051401:Aquaporin 4; D005904:Glial Fibrillary Acidic Protein; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; C035267:glycoprotein 40 antigen, human; D014867:Water