Role of protein kinase C in cyclic AMP-mediated suppression of T-lymphocyte activation following burn injury

Martin G. Schwacha, Alfred Ayala, William G. Cioffi, Kirby I. Bland, Irshad H. Chaudry

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Major burn injury induces T-lymphocyte dysfunction. Previous studies suggest that prostaglandin (PG) E2, which is elevated post-burn, is the causative factor via a cyclic AMP-dependent process. The present study was conducted to elucidate the mechanism by which cAMP induces T-lymphocyte dysfunction following burn injury. Splenocytes were isolated from mice 7 days after receiving a scald burn covering 25% of their total body surface or sham procedure. ConA-induced proliferation by splenocytes from burned mice was significantly suppressed. Macrophage depletion of the splenocyte cultures abrogated the suppression. Concanavalin A-stimulated proliferation by macrophage-depleted splenocytes was suppressed by PGE2 and dibutyryl cAMP in both groups. The IC50 of these cAMP-elevating agents, however, was approximately 100-fold lower for cells from burned mice, indicating an increased sensitivity to cAMP. PGE2 did not suppress PMA/Ca2+ ionophore-induced T-lymphocyte activation. Addition of PMA to ConA-stimulated cultures prevented the suppression of proliferative responses by PGE2, whereas Ca2+ ionophore had no effect. Thus, the suppression of T-lymphocyte activation following burn injury is macrophage-dependent, related to an increased sensitivity to cAMP and due to an uncoupling of cell surface receptors from protein kinase C activation. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)45-53
Number of pages9
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1455
Issue number1
DOIs
StatePublished - Sep 20 1999
Externally publishedYes

Keywords

  • Immunosuppression
  • Macrophage
  • Prostaglandin E
  • Signal transduction
  • Thermal injury

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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