Complement-dependent bystander injury to neurons in AQP4-IgG seropositive neuromyelitis optica

• DOI: 10.1186/s12974-018-1333-z
• Publication Date: 2018-10-22T13:30:27Z
• Authors: Tianjiao Duan; Alex J. Smith; Alan S. Verkman
• Keywords: Neuromyelitis Optica; Aquaporin 4; Bystander effect

Aquaporin-4-immunoglobulin G (AQP4-IgG) seropositive neuromyelitis optica spectrum disorder (herein called NMO) is an autoimmune disease of the central nervous system in which AQP4-IgG binding to AQP4 on astrocytes results complement-dependent astrocyte injury and secondary inflammation, demyelination, neuron loss. We previously reported evidence for a complement bystander mechanism early oligodendrocyte NMO. Herein, we tested hypothesis that injury, involves diffusion nearby cells activated soluble components from complement-injured astrocytes, general phenomenon may contribute neuronal NMO.Primary cocultures rat cortical neurons were established study cell death after exposure complement. In animal experiments, was delivered adult rats by intracerebral injection. Cell cultures brain studied immunofluorescence.In primary astrocyte-neuron cocultures, addition resulted astrocytes. Deposition membrane attack complex C5b-9 seen whereas C1q, initiating protein pathway, only Neuron not with inhibitor, C1q- or C6-depleted complement, pure exposed toxin. Intracerebral injection fixable dead fluorescent marker produced near deposition. receiving inhibitor AQP4-IgG-injected knockout rats.These support novel NMO provide be following AQP4-IgG-targeted death.