Platelet activating factor receptor binding plays a critical role in jet fuel-induced immune suppression

Gerardo Ramos, Nasser Kazimi, Dat X. Nghiem, Jeffrey P. Walterscheid, Stephen E. Ullrich

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Applying military jet fuel (JP-8) or commercial jet fuel (Jet-A) to the skin of mice suppresses the immune response in a dose-dependant manner. The release of biological response modifiers, particularly prostaglandin E 2 (PGE2), is a critical step in activating immune suppression. Previous studies have shown that injecting selective cyclooxygenase-2 inhibitors into jet fuel-treated mice blocks immune suppression. Because the inflammatory phospholipid mediator, platelet-activating factor (PAF), up-regulates cyclooxygenase-2 production and PGE2 synthesis by keratinocytes, we tested the hypothesis that PAF-receptor binding plays a role in jet fuel-induced immune suppression. Treating keratinocyte cultures with PAF and/or jet fuel (JP-8 and Jet-A) stimulates PGE2 secretion. Jet fuel-induced PGE2 production was suppressed by treating the keratinocytes with specific PAF-receptor antagonists. Injecting mice with PAF, or treating the skin of the mice with JP-8, or Jet-A, induced immune suppression. Jet fuel-induced immune suppression was blocked when the jet fuel-treated mice were injected with PAF-receptor antagonists before treatment. Jet fuel treatment has been reported to activate oxidative stress and treating the mice with anti-oxidants (Vitamins C, or E or beta-hydroxy toluene), before jet fuel application, interfered with immune suppression. These findings confirm previous studies showing that PAF-receptor binding can modulate immune function. Furthermore, they suggest that PAF-receptor binding may be an early event in the induction of immune suppression by immunotoxic environmental agents that target the skin.

Original languageEnglish (US)
Pages (from-to)331-338
Number of pages8
JournalToxicology and Applied Pharmacology
Volume195
Issue number3
DOIs
StatePublished - Mar 15 2004
Externally publishedYes

Keywords

  • BHT
  • Beta-hydroxy toluene
  • Carbamyl platelet-activating factor
  • Commercial jet fuel
  • DTH
  • Delayed-type hypersensitivity
  • Immune suppression
  • JP-8
  • Jet fuel
  • Jet propulsion-8 military jet fuel
  • Jet-A
  • Oct Br.
  • Platelet-activating factor
  • Prostaglandins
  • c-PAF

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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