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

45 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)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume282
Issue number5 51-5
Publication statusPublished - 2002

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Keywords

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

ASJC Scopus subject areas

  • Physiology

Cite this

Carlson, D. L., Lightfoot, E., Bryant, D. D., Haudek, S. B., Maass, D., Horton, J., & Giroir, B. P. (2002). Burn plasma mediates cardiac myocyte apoptosis via endotoxin. American Journal of Physiology - Heart and Circulatory Physiology, 282(5 51-5).