Filep János G, Khreiss Tarek, József Levente
Research Center, Maisonneuve-Rosemont Hospital, University of Montreal, 5415 boulevard de l'Assomption, Montreal, Que., Canada H1T 2M4.
Prostaglandins Leukot Essent Fatty Acids. 2005 Sep-Oct;73(3-4):257-62. doi: 10.1016/j.plefa.2005.05.014.
Lipoxin A4 (LXA4) and aspirin-triggered 15-epi-LXA4 (ATL) are emerging as endogenous braking signals for neutrophil-mediated tissue injury. LXA4 and ATL and their metabolically stable analogues display potent inhibitory actions in human isolated cells and blood, including attenuation of expression of adhesion molecules on leukocytes and endothelial cells, neutrophil adhesion to endothelial cells and platelets under shear, and IL-8 production, key events of the acute inflammatory response. The underlying molecular mechanisms include interference with MAPK signaling pathways, modulation of the oxidative chemistry of superoxide, NO and ONOO-, inhibition of activation of NF-kappaB and AP-1, and consequently the expression of interleukin-8 and likely other pro-inflammatory genes. Collectively, these results add to the profile of LXA4/ATL rapid actions that contribute to "stop signaling" involved in regulating neutrophil functions during acute inflammation and suggest that aspirin inhibits neutrophil accumulation through triggering the synthesis of 15-epi-LXA4.
脂氧素A4（LXA4）和阿司匹林触发的15-表-LXA4（ATL）正逐渐成为中性粒细胞介导的组织损伤的内源性制动信号。LXA4和ATL及其代谢稳定类似物在人分离细胞和血液中表现出强大的抑制作用，包括减弱白细胞和内皮细胞上黏附分子的表达、在剪切力作用下中性粒细胞与内皮细胞和血小板的黏附以及IL-8的产生，这些都是急性炎症反应的关键事件。潜在的分子机制包括干扰丝裂原活化蛋白激酶（MAPK）信号通路、调节超氧化物、一氧化氮（NO）和过氧亚硝酸盐（ONOO-）的氧化化学性质、抑制核因子κB（NF-κB）和活化蛋白-1（AP-1）的激活，从而抑制白细胞介素-8以及可能其他促炎基因的表达。总的来说，这些结果丰富了LXA4/ATL快速作用的特征，这些作用有助于在急性炎症期间调节中性粒细胞功能的“停止信号”，并表明阿司匹林通过触发15-表-LXA4的合成来抑制中性粒细胞的聚集。
