Enhanced Platelet-Activating Factor Synthesis Facilitates Acute and Delayed Effects of Ethanol-Intoxicated Thermal Burn Injury

Kathleen A. Harrison, Eric Romer, Jonathan Weyerbacher, Jesus A. Ocana, Ravi P. Sahu, Robert C. Murphy, Lisa E. Kelly, Townsend A. Smith, Christine M. Rapp, Christina Borchers, David R. Cool, Gengxin Li, Richard Simman, Jeffrey B. Travers

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Thermal burn injuries in patients who are alcohol-intoxicated result in greater morbidity and mortality. Murine models combining ethanol and localized thermal burn injury reproduce the systemic toxicity seen in human subjects, which consists of both acute systemic cytokine production with multiple organ dysfunction, as well as a delayed systemic immunosuppression. However, the exact mechanisms for these acute and delayed effects are unclear. These studies sought to define the role of the lipid mediator platelet-activating factor in the acute and delayed effects of intoxicated burn injury. Combining ethanol and thermal burn injury resulted in increased enzymatic platelet-activating factor generation in a keratinocyte cell line in vitro, human skin explants ex vivo, as well as in murine skin in vivo. Further, the acute increase in inflammatory cytokines, such as IL-6, and the systemic immunosuppressive effects of intoxicated thermal burn injury were suppressed in mice lacking platelet-activating factor receptors. Together, these studies provide a potential mechanism and treatment strategies for the augmented toxicity and immunosuppressive effects of thermal burn injury in the setting of acute ethanol exposure, which involves the pleotropic lipid mediator platelet-activating factor.

Original languageEnglish (US)
Pages (from-to)2461-2469
Number of pages9
JournalJournal of Investigative Dermatology
Volume138
Issue number11
DOIs
StatePublished - Nov 2018
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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    Harrison, K. A., Romer, E., Weyerbacher, J., Ocana, J. A., Sahu, R. P., Murphy, R. C., Kelly, L. E., Smith, T. A., Rapp, C. M., Borchers, C., Cool, D. R., Li, G., Simman, R., & Travers, J. B. (2018). Enhanced Platelet-Activating Factor Synthesis Facilitates Acute and Delayed Effects of Ethanol-Intoxicated Thermal Burn Injury. Journal of Investigative Dermatology, 138(11), 2461-2469. https://doi.org/10.1016/j.jid.2018.04.039