Lipoxins and aspirin-triggered 15-epi-lipoxin biosynthesis: an update and role in anti-inflammation and pro-resolution

Abstract

Lipoxins (LX) are trihydroxytetraene-containing eicosanoids that are generated within the vascular lumen during platelet–leukocyte interactions and at mucosal surfaces via leukocyte-epithelial cell interactions. Recent findings have given several new concepts that are reviewed here regarding the generation of LX and 15 epi-LX and their impact in the resolution of acute inflammation and organ protection from leukocyte-mediated injury. During cell–cell interactions, transcellular biosynthetic pathways are used as major LX biosynthetic routes, and thus, in humans, LX are formed in vivo during multicellular responses such as inflammation, and asthma. This branch of the eicosanoid cascade generates specific tetraene-containing products that serve as neutrophil “stop signals,” in that they regulate key steps in leukocyte trafficking and prevent neutrophil-mediated acute tissue injury. In addition, aspirin’s mechanism of action also involves the triggering of carbon 15 epimers of lipoxins or 15-epi-lipoxins that mimic the bioactions of native LX. An overview of these recent developments is presented with a focus on the cellular and molecular interactions of these novel anti-inflammatory lipid mediators that also appear to facilitate the resolution of acute inflammatory responses.