Serum-dependence of LPS-induced neurotoxicity in rat cortical neurons

Previous studies have shown that the bacterial endotoxin, lipopolysaccharide (LPS), is neurotoxic both in vitro and in vivo. The rate of binding of LPS to a target cell is greatly enhanced by serum in general and by LPS binding protein (LBP) in particular. The purpose of the study described in this paper was to determine if microglia activation and LPS-induced neurotoxicity is serum or LBP dependent. A murine microglial cell line, BV2, was used to assess the serum dependence of nitric oxide production and tumor necrosis factor a release in microglia. Embryonic rat cortical neuron/glia mixed cultures were used to determine the serum dependence of LPS-induced neurotoxicity. Our results from both cell culture systems show that LPS-induced inflammatory responses are serum dependent at lower doses of LPS and progressively become serum independent above 10 ng/ml. Purified human recombinant LBP reconstitutes the lost LPS-induced inflammatory responses in primary and immortalized cell cultures treated with heat-denatured serum and appears to account for the serum dependence. These data suggest that the cell surface signaling receptor for LPS at the low and high concentrations are likely to differ, consistent with the existence of a variety of LPS receptors.