Ramos Gerardo, Kazimi Nasser, Nghiem Dat X, Walterscheid Jeffrey P, Ullrich Stephen E
Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Toxicol Appl Pharmacol. 2004 Mar 15;195(3):331-8. doi: 10.1016/j.taap.2003.07.014.
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.
将军用喷气燃料（JP - 8）或商用喷气燃料（Jet - A）涂抹于小鼠皮肤会以剂量依赖的方式抑制免疫反应。生物反应调节剂的释放，尤其是前列腺素E2（PGE2），是激活免疫抑制的关键步骤。先前的研究表明，向经喷气燃料处理的小鼠注射选择性环氧化酶 - 2抑制剂可阻断免疫抑制。由于炎症性磷脂介质血小板活化因子（PAF）可上调角质形成细胞中环氧化酶 - 2的产生和PGE2的合成，我们测试了PAF受体结合在喷气燃料诱导的免疫抑制中起作用的假设。用PAF和/或喷气燃料（JP - 8和Jet - A）处理角质形成细胞培养物会刺激PGE2分泌。用特异性PAF受体拮抗剂处理角质形成细胞可抑制喷气燃料诱导的PGE2产生。给小鼠注射PAF，或用JP - 8或Jet - A处理小鼠皮肤，会诱导免疫抑制。在处理前给经喷气燃料处理的小鼠注射PAF受体拮抗剂，可阻断喷气燃料诱导的免疫抑制。据报道，喷气燃料处理会激活氧化应激，在应用喷气燃料之前用抗氧化剂（维生素C、维生素E或β - 羟基甲苯）处理小鼠会干扰免疫抑制。这些发现证实了先前的研究，即PAF受体结合可调节免疫功能。此外，它们表明PAF受体结合可能是靶向皮肤的免疫毒性环境因子诱导免疫抑制过程中的早期事件。
