ACTIVATION OF ARACHIDONIC-ACID METABOLISM IN MOUSE MACROPHAGES BY BACTERIAL AMPHIPHILES

The relative activities of lipoteichoic acid (LTA) from four Gram-posi tive bacteria were compared to different lipopolysaccharide (LPS) prep arations for activation of arachidonic acid metabolism in mouse perito neal macrophages. Total eicosanoid was determined in cultures labeled with [H-3]-arachidonic acid. Prostaglandin E(2) (PGE(2)) and leukotrie ne C-4. (LTC(4)) were determined by EIA analysis, The relative potenci es of the different preparations were: smooth LPS from Salmonella abor tus greater than or equal to Re-LPS from Salmonella minnesota (R-595) greater than or equal to LTA from Streptococcus pyogenes approximate t o Streptococcus faecalis approximate to Staphylococcus aureus greater than or equal to monophosphoryl lipid A derived from the Re-LPS > > LT A from Bacillus subtilis. Activation of eicosanoid release was inhibit ed by staurosporin for all of the amphiphiles tested, Treatment of the macrophage cultures with LTA from S. pyogenes, S. faecalis, and S. au reus, either in the presence or absence of indomethacin, desensitized the cells to eicosanoid release on subsequent challenge with LPS, The desensitized cells remained responsive to the phorbol ester phorbol my ristate acetate. LPS from Gram-negative bacteria has immunostimulatory and endotoxic activities which result, in part, from the release of e icosanoids and other mediators from activated macrophages. The similar ities in the patterns of cell activation by LPS and LTA suggest that l ipoteichoic acids might contribute to the pathogenicities of Gram-posi tive bacteria.