Glia cell response to bacterial lipopolysaccharide: Effect on nucleotide synthesis, its genetic control and definition of the active principle

Cell types sensitive to lipopolysaccharides (LPS) include macrophages, polymorphonuclear leukocytes, platelets, B-lymphocytes and fibroblasts. Earlier observations that during endotoxemia or intracerebral injection of LPS morphological and functional alterations of the central nervous system develop, suggest that LPS may also interact with brain cells. The effects of bacterial products on nucleotide synthesis of cultured murine glia cells are examined in this study. LPS extracted from the outher cell wall of gram-negative bacteria were found to cause an increased RNA synthesis and an inhibition of DNA synthesis in the cultured glia cells. The inhibitory effect of LPS on DNA synthesis is not due to an LPS-mediated increase of the cAMP content in the glia cells or contact inhibition of the monolayer culture. Within the structure of LPS lipid A was found to be the active part. On the basis of the LPS-induced increase of RNA synthesis, the glia cells of C3H/HeJ mice are low responders to low dosis of LPS. We conclude that in the presence of fetal calf serum glia cells are sensitive to the lipid A part of LPS, the sensitivity being under genetic control.