Serhan C N
Center for Experimental Therapeutics and Reperfusion Injury, Brigham, and Women's Hospital, Boston, Massachusetts 02115, USA.
Prostaglandins. 1997 Feb;53(2):107-37. doi: 10.1016/s0090-6980(97)00001-4.
Lipid-derived mediators play critical roles in inflammation and other multicellular vascular processes, including atherosclerosis and thrombosis. The lipoxins (LXs) were first isolated in 1984, and have continued to show intriguing and potentially important biological roles. These compounds carry a trihydroxytetraene structure and are both structurally and functionally unique among arachidonic acid-derived bioactive products. The availability of synthetic materials for evaluation of bioactions as well as appropriate methods of detection to determine when and where LX are generated has, in recent studies, catapulted our understanding of the formation and actions of the lipoxins. This mini-review addresses new concepts in the formation and biological roles of these lipid-derived mediators and considers whether the lipoxins and the newly discovered aspirin-triggered lipoxins (ATL) represent novel approaches for therapeutic opportunities. Recent findings indicate that select cytokines and aspirin initiate and regulate LX biosynthetic events. These circuits involve cell-cell interfacing that facilitates transcellular events to form LX that display anti-inflammatory actions in both in vitro and in vivo models. These recent results suggest that LX biosynthetic circuits assemble to evoke anti-inflammatory actions and generate LX that can serve as "stop signals" in appropriate microenvironments.
脂质衍生介质在炎症和其他多细胞血管过程中发挥着关键作用，包括动脉粥样硬化和血栓形成。脂氧素（LXs）于1984年首次被分离出来，并持续展现出引人入胜且可能具有重要意义的生物学作用。这些化合物具有三羟基四烯结构，在花生四烯酸衍生的生物活性产物中，其结构和功能均独一无二。在最近的研究中，用于评估生物活性的合成材料的可得性以及用于确定LX生成时间和位置的合适检测方法，极大地推动了我们对脂氧素形成和作用的理解。这篇小型综述探讨了这些脂质衍生介质形成和生物学作用的新概念，并思考脂氧素和新发现的阿司匹林触发脂氧素（ATL）是否代表了新的治疗机会。最近的研究结果表明，特定的细胞因子和阿司匹林启动并调节LX的生物合成过程。这些过程涉及细胞间的相互作用，促进跨细胞事件以形成在体外和体内模型中均显示抗炎作用的LX。这些最新结果表明，LX生物合成过程聚集在一起引发抗炎作用，并产生可在适当微环境中充当“终止信号”的LX。
