Role of AQP4 in the developmnet of Neuromyelitis Optica (NMO)

CLAUDIA CAPURRO

Jornada; Jornada Italo-Argentina de la Scuola di Studi Superiori del CUIA in ?Bioscienze e Biotecnologie?; 2013

NMO-IgG autoantibody selectively binds to Aquaporin-4 (AQP4), the most abundant water channel in the central nervous system, and is now considered an useful serum biomarker of neuromyelitis optica (NMO). A series of clinical and pathological observations suggest that NMO-IgG may play a central role in NMO physiopathology. In the current study we evaluated, in well-differentiated astrocytes cultures, the consequences of NMO-IgG binding on the expression pattern of AQP4 and on its water permeability. Cells were exposed to inactivated sera in two very different situations: 1 hour at 4°C (to restrict membrane fluidity) or 12 hours 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 fluorescence videomicroscopy technique. Our results showed that at low temperature, exposition of cells to control or NMO-IgG sera does not affect neither AQP4 expression nor the water permeability of the plasma membrane. However, long-term exposition to NMO-IgG at 37 °C induced a loss of human IgG signal from the plasma membrane together with changes in the pattern of expression of AQP4 and a significant reduction of the 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.