Staphylococcal Glycocalyx Activates Macrophage Prostaglandin E2 and Interleukin 1 Production and Modulates Tumor Necrosis Factor Alpha and Nitric Oxide Production

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We have examined the effect of staphylococcal glycocalyces on the ability of murine peritoneal macrophages to produce prostaglandin E2 (PGE2) and the inflammatory cytokines interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF-α) and to generate nitric oxide. Glycocalyx partially purified under endotoxin-free conditions from defined liquid medium cultures of Staphylococcus lugdunensis or Staphylococcus epidermidis was a strong stimulator of PGE2 and IL-1 production. The addition of 10 to 100 μg of glycocalyx per ml induced levels of IL-1 and PGE2 production similar to that induced by 0.1 to 1 μg of Escherichia coli lipopolysaccharide (LPS) per ml. In contrast, glycocalyx induced ninefold less TNF-α and three- to fourfold less nitrite than LPS. A modulatory effect was suggested by the observation that the amount of TNF-α and nitrite generated remained constant whether the macrophages were stimulated with 10 or 100 μg of glycocalyx per ml. A selective modulation of macrophage activation was confirmed by the demonstration that costimulation of macrophages with both glycocalyx and LPS resulted in a reduction in TNF-α and nitrite generation relative to stimulation with LPS alone even though costimulation had no effect on PGE2 production and increased IL-1 production. Involvement of PGE2 in this modulatory effect was suggested by the ability of indomethacin to augment glycocalyx-stimulated TNF-α production and to reverse the inhibitory effect of glycocalyx on LPS induction of TNF-α production. However, the inability of indomethacin to reverse the inhibitory effect of glycocalyx on LPS- induced nitric oxide generation suggests that the selective modulation of macrophage function by glycocalyx may be more complex than increased sensitivity to PGE2 feedback inhibition.