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

The relative activities of lipoteichoic acid (LTA) from four Gram-positive bacteria were compared to different lipopolysaccharide (LPS) preparations for activation of arachidonic acid metabolism in mouse peritoneal macrophages. Total eicosanoid was determined in cultures labeled with [H-3]-arachidonic acid. Prostaglandin E(2) (PGE(2)) and leukotriene C-4. (LTC(4)) were determined by EIA analysis, The relative potencies of the different preparations were: smooth LPS from Salmonella abortus greater than or equal to Re-LPS from Salmonella minnesota (R-595) greater than or equal to LTA from Streptococcus pyogenes approximate to Streptococcus faecalis approximate to Staphylococcus aureus greater than or equal to monophosphoryl lipid A derived from the Re-LPS > > LTA from Bacillus subtilis. Activation of eicosanoid release was inhibited by staurosporin for all of the amphiphiles tested, Treatment of the macrophage cultures with LTA from S. pyogenes, S. faecalis, and S. aureus, 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 myristate acetate. LPS from Gram-negative bacteria has immunostimulatory and endotoxic activities which result, in part, from the release of eicosanoids and other mediators from activated macrophages. The similarities in the patterns of cell activation by LPS and LTA suggest that lipoteichoic acids might contribute to the pathogenicities of Gram-positive bacteria.