POTENTIAL VASCULAR ROLES FOR LIPOXINS IN THE STOP PROGRAMS OF HOST-DEFENSE AND INFLAMMATION

Eicosanoids are oxygenated products of arachidonic acid or other relat ed 20-carbon polyunsaturated fatty acids that modulate diverse biologi c processes, including leukocyte recruitment and activation, hemostasi s, blood flow ion transport, smooth muscle contraction mucous secretio n, cell growth, and stimulus-response coupling. Inflammatory, thrombot ic, and ischemic vascular events are complex multicellular responses t hat involve interactions of circulating blood cells with each other an d with components of the vessel wall. Here, we review evidence that li poxygenase-derived eicosanoids, specifically leukotrienes (LT) and lip oxins (LX), ave generated within the vascular lumen during cell-cell i nteractions in inflammation and thrombosis. Transcellular biosynthetic pathways appear to be rich sources of LT and LX in these settings and may amplify the away and levels of lipid-derived mediators generated within a local vascular milieu. Cytokines and cell-cell adhesion can p romote transcellular eicosanoid generation by amplifying pivotal enzym atic events in lipoxygenase biosynthetic pathways and facilitating tra nsfer of relatively unstable lipophilic lipoxygenase-derived intermedi ates between cells. Leukotrienes are well-established proinflammatory mediators and stimuli for leukocyte recruitment and activation, plasma exudation, and smooth muscle contraction. Lipoxins, a more recent add ition to the families of eicosanoids, inhibit LT-induced polymorphonuc lear neutrophil (PMN) chemotaxis, adhesion to endothelial cells, diape desis, vasoconstriction, and bronchoconstriction in several model syst ems and ave potential modulators of LT bioactivity that may serve to l imit PMN-mediated tissue injury in host defense, inflammation, ischemi a-reperfusion, hemostasis, and other vascular events.