Astrocytic S100B Protein Modulates Glutamate Uptake and Neutrophil Migration in Vitro

Astrocytic S100B protein has widely been used as a peripheral reporter of blood-brain barrier dysfunction and as a marker of brain damage. Once secreted/released, S100B exerts autocrine and paracrine effects on responsive cells by engaging the receptor for advanced glycation end products (RAGE). However, high levels of S100B cause free radical damage via RAGE activation and trigger neuroinflammation. Significantly high levels of S100B have been reported in the serum and cerebrospinal fluid after West Nile infection. Since viral infection mediated impairment in the glutamate transport across astrocytes has also been shown, we explored in the present study if S100B has a role in modulating glutamate uptake and neutrophil migration in vitro. The effects of S100B on cultured astrocytic cell lines or primary cultures were studied using immunocytochemical, morphometric and radioactive glutamate uptake techniques. With increasing concentration of S100B, we found significantly decreased glutamate uptake in C8 and primary astrocytes with an exception that lower concentration (10 nM) of S100B promoted glutamate uptake in C8 cells. Moreover, neutrophils isolated from the mouse bone marrow and treated with S100B showed a dose-dependent increase in migration across the membrane insert. Conversely, the anti-S100B antibody inhibited the S100B-induced neutrophil migration. We conclude that high levels of S100B in the brain or systemic circulation may stimulate neuroinflammation and impair glutamate reuptake into astrocytes causing neurotoxicity.