Burn plasma mediates cardiac myocyte apoptosis via endotoxin

Deborah L. Carlson, Ellis Lightfoot, Debora D. Bryant, Sandra B. Haudek, David Maass, Jureta Horton, Brett P. Giroir

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

Thermal trauma is associated with cardiac myocyte apoptosis in vivo. To determine whether cardiac myocyte apoptosis could be secondary to burn-induced cytokines or inflammatory mediators, we investigated the effects of tumor necrosis factor-α (TNF-α) and burn plasma on a murine cardiac myocyte cell line and primary culture myocytes. HL-1 cells were exposed to plasma isolated from burned or sham rats. Burn, but not sham plasma, induced significant increases in caspase-3 activity and DNA fragmentation. Similar results were obtained in primary culture rat myocytes. A dose-dependent increase in caspase-3 activity was observed when HL-1 cells were incubated with increasing concentrations of TNF-α. Even though TNF-α increased apoptosis, enzyme-linked immunosorbent assay detected no TNF-α in burn plasma. Burn plasma also failed to induce TNF-α mRNA, eliminating an autocrine mechanism of TNF-α secretion and binding. Also, treatment of burn plasma containing rhuTNFR:Fc failed to inhibit apoptosis. To examine the possibility that endotoxin within burn plasma might account for the apoptotic effect, burn plasma was preincubated with rBPI21. Caspase-3 activity was reduced to control levels. These data indicate that burn plasma induces apoptosis in cardiac myocytes via an endotoxin-dependent mechanism and suggest that systemic inhibition of endotoxin may provide a therapeutic approach for treatment of burn-associated cardiac dysfunction.

Original languageEnglish (US)
Pages (from-to)H1907-H1914
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume282
Issue number5 51-5
DOIs
StatePublished - 2002

Keywords

  • Caspase-3
  • Enzyme-linked immunosorbent assay
  • Thermal trauma
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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