STAPHYLOCOCCAL GLYCOCALYX ACTIVATES MACROPHAGE PROSTAGLANDIN E(2) ANDINTERLEUKIN-1 PRODUCTION AND MODULATES TUMOR-NECROSIS-FACTOR-ALPHA AND NITRIC-OXIDE PRODUCTION

We have examined the effect of staphylococcal glycocalyces on the abil ity of murine peritoneal macrophages to produce prostaglandin E(2) (PG E(2)) and the inflammatory cytokines interleukin 1 (IL-1) and tumor ne crosis factor alpha (TNF-alpha) and to generate nitric oxide. Glycoaly x partially purified under endotoxin-free conditions from defined liqu id medium cultures of Staphylococcus lugdunensis or Staphylococcus epi dermidis was a strong stimulator of PGE(2) and IL-1 production. The ad dition of 10 to 100 mu g of glycocalyx per ml induced levels of IL-1 a nd PGE(2) production similar to that induced by 0.1 to 1 mu g of Esche richia coli lipopolysaccharide (LPS) per ml. In contrast, glycocalyx i nduced ninefold less TNF-alpha and three- to fourfold less nitrite tha n LPS. A modulatory effect was suggested by the observation that the a mount of TNF-alpha and nitrite generated remained constant whether the macrophages were stimulated with 10 or 100 mu g of glycocalyx per ml. A selective modulation of macrophage activation was confirmed by the demonstration that costimulation of macrophages with both glycocalyx a nd LPS resulted in a reduction in TNF-alpha and nitrite generation rel ative to stimulation with LPS alone even though costimulation had no e ffect on PGE(2) production and increased IL-l production. Involvement of PGE(2) in this modulatory effect was suggested by the ability of in domethacin to augment glycocalyx-stimulated TNF-alpha production and t o reverse the inhibitory effect of glycocalyx on LPS induction of TNF- alpha production. However, the inability of indomethacin to reverse th e inhibitory effect of glycocalyx on LPS-induced nitric oxide generati on suggests that the selective modulation of macrophage function by gl ycocalyx may be more complex than increased sensitivity to PGE(2) feed back inhibition.