Escherichia-coli lipopolysaccharide enhances the release of a no-like factor from astrocytoma-cells in culture

An 18 h coincubation of a human astrocytoma cell line (GO-G-UVW) with E. coli lipopolysaccharide (LPS) significantly increased nitrite concentrations in cell culture medium and potentiated the inhibition of human washed thrombin-induced platelet aggregation produced solely by astrocytoma cells. This was due to the increased release from astrocytoma cells of nitric oxide (NO) or a NO-like substance, since it was prevented by oxyhemoglobin (OxyHb), a trapping agent for NO, and potentiated by superoxide dismutase (SOD), which enhances the biological effects of NO through the removal of superoxide anions. In addition, the NO-like factor released by astrocytoma cells seems to originate from L-arginine, since its anti-aggregatory properties, as well as nitrite generation in astrocytoma cells culture medium, were blocked by incubating cells with N(G)-monomethyl-L-arginine, a selective inhibitor of NO synthase. These effects were restored by L-arginine, the precursor of NO, but not by D-arginine. In conclusion, the present experiments show that LPS is able to increase the release of NO or a NO-like substance from glial cells and suggest that, under conditions in which high levels of endotoxin are present (septic shock, severe infections), or under some pathological conditions accompanied by an abnormal permeability of the blood brain barrier, NO released from glial cells may affect neuronal activity in the brain.