Figure 6.

Anti-aquaporin-4 (AQP4) Ab binding astrocytes initiate two parallel complementary reactions. The first one is dependent on the complement cytotoxicity via C5b-9 complex formation (pathway 3.–3a.1.–4a.), and the second one on the sublytic effect of C5b-9 and dysregulation of astrocyte glutamate pump into extracellular space by C5a-preactivated neutrophils (pathway 3.–3a.2.–3b.–3c.–3d.–4b.). As a consequence, astrocytes are partially destroyed; however, a major population of astrocytes polarizes into proinflammatory cells which produce cytokines and chemokines and are characterized by pathological glutamate removal from extracellular space.