Lipoxins: putative braking signals in host defense, inflammation and hypersensitivity

Lipoxins are arachidonate-derived lipid mediators that are structurally and functionally distinct from other classes of eicosanoids. They are generated via transcellular pathways that initially involve the dual lipoxygenation of arachidonic acid either by 15- and 5-lipoxygenases or by 5- and 1.2-lipoxygenases (lipoxygenase interaction products). Platelet-neutrophil interactions are a particularly rich source of lipoxins within the vascular lumen. Cell-cell adhesion and cytokines are important amplifiers of these complex biosynthetic circuits. Leukocytes and endothelial cells express high affinity receptors for lipoxins, engagement of which evokes a unique profile of signal transduction events and bioactivities. In many assay systems, lipoxins prevent chemotaxis, adhesion, and transmigration of neutrophils induced by leukotrienes and other mediators, suggesting that lipoxins may act as endogenous braking signals in host defense, inflammation, and hypersensitivity reactions. Intriguingly, cyclo-oxygenase II, in the presence of aspirin, catalyses the formation of a novel series of 15-epi-lipoxins during neutrophil-endothelial cell interactions, suggesting a new mechanism of action for this commonly used therapeutic agent.