Formation of endogenous "antiinflammatory" lipid mediators by transcellular biosynthesis. Lipoxins and aspirin-triggered lipoxins inhibit neutrophil recruitment and vascular permeability.

Neutrophil-dependent vascular injury gives rise to increased vascular permeability, edema, and further release of chemoattractants. Leukotriene B 4 (LTB 4 ) is among the most potent neutrophil stimuli and thus participates in tissue injury via recruiting neutrophils (PMNs, polymorphonuclear leukocytes) in pathophysiologic scenarios (1). Lipoxins are trihydroxytetraene-containing eicosanoids that are, among other in vivo sites, also generated within vascular lumen primarily by platelet-leukocyte interactions by pathways (Figure 1) that are activated during multicellular responses such as inflammation, atherosclerosis, and thrombosis (for a review, see Reference 2). In addition, aspirin has been found to trigger the transcellular biosynthesis of a new group of compounds termed 15-epi-lipoxins (15-epi-LXs) or aspirin-triggered lipoxins, which are likely to contribute to some of the beneficial actions ascribed to aspirin by serving as local endogenous antiinflammatory lipid mediators (2). Thus, these LX branches illustrated in Figure 1 involve cell-cell interactions that appear to produce endogenous stop signals or antiinflammatory compounds, while the 5-lipoxygenase pathway generates leukotrienes that evoke cellular events that are considered to be proinflammatory.