title: Platelet activating factor receptor binding plays a critical role in jet fuel-induced immune suppression.
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-dependent manner. The release of biological response modifiers, particularly prostaglandin E2 (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.
authors.affiliation: Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Ramos
authors.forename: Nasser
authors.initials: N
authors.lastname: Kazimi
authors.forename: Dat X
authors.initials: DX
authors.lastname: Nghiem
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Walterscheid
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Ullrich
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D001205:Ascorbic Acid / Q000627:therapeutic use; D002460:Cell Line; D015232:Dinoprostone / Q000032:analysis / Q000276:immunology; D005260:Female; D006838:Hydrocarbons / Q000633:toxicity*; D006968:Hypersensitivity, Delayed / Q000139:chemically induced* / Q000188:drug therapy / Q000276:immunology; D015603:Keratinocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D010972:Platelet Activating Factor / Q000031:analogs & derivatives / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D014810:Vitamin E / Q000627:therapeutic use
chemical_list: D006838:Hydrocarbons; C098607:JP8 aviation fuel; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D014810:Vitamin E; C029662:JP5 jet fuel; D015232:Dinoprostone; D001205:Ascorbic Acid