Thermal injury alters macrophage responses to prostaglandin E2: Contribution to the enhancement of inducible nitric oxide synthase activity

Academic Article


  • Prostaglandin E2 (PGE2) and macrophage (Mφ) -derived reactive nitrogen intermediates (RNI) have been implicated in T cell dysfunction after thermal injury. Normally, Mφ inducible nitric oxide synthase (iNOS) activity can be regulated by PGE2, however, it is unknown whether PGE2 modulates Mφ iNOS activity after thermal injury. Splenic Mφ isolated from mice 7 days after thermal injury produced higher levels of RNI than Mφ from sham mice when stimulated with lipopolysaccharide (LPS) or interferon-γ (IFN-γ) and tumor necrosis factor α (TNF-α) in combination. PGE2, when added concurrently with LPS, suppressed RNI production by Mφ from sham mice, whereas Mφ from injured mice were unaffected. When Mφ were pretreated with PGE2 before LPS, RNI production was suppressed in both populations. RNI production in response to IFN-γ or IFN-γ and TNF-α in combination was enhanced by PGE2 in both populations, however, the effect was markedly greater in Mφ from injured mice. The PGE2-mediated changes in RNI production were paralleled by similar changes in iNOS protein expression, suggesting that the effect of PGE2 was at the level of enzyme expression rather than activity. Dibutryl cAMP induced similar effects as PGE2, suggesting the response to PGE2 after thermal injury is independent of potential changes in PGE2-induced adenylate cyclase activity and is cAMP- mediated. The results indicate that Mφ from burned mice display an altered sensitivity to PGE2, resulting in enhanced iNOS activity. Thus, PGE2, which is elevated after thermal injury and can directly suppress T cell function, may also contribute to immune dysfunction through the enhancement of Mφ iNOS activity.
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    Digital Object Identifier (doi)

    Author List

  • Schwacha MG; Samy TSA; Catania RA; Chaudry IH
  • Start Page

  • 740
  • End Page

  • 746
  • Volume

  • 64
  • Issue

  • 6