title: Potential vascular roles for lipoxins in the "stop programs" of host defense and inflammation.
abstract: Eicosanoids are oxygenated products of arachidonic acid or other related 20-carbon polyunsaturated fatty acids that modulate diverse biologic processes, including leukocyte recruitment and activation, hemostasis, blood flow, ion transport, smooth muscle contraction, mucous secretion, cell growth, and stimulus-response coupling. Inflammatory, thrombotic, and ischemic vascular events are complex multicellular responses that involve interactions of circulating blood cells with each other and with components of the vessel wall. Here, we review evidence that lipoxygenase-derived eicosanoids, specifically leukotrienes (LT) and lipoxins (LX), are generated within the vascular lumen during cell-cell interactions in inflammation and thrombosis. Transcellular biosynthetic pathways appear to be rich sources of LT and LX in these settings and may amplify the array and levels of lipid-derived mediators generated within a local vascular milieu. Cytokines and cell-cell adhesion can promote transcellular eicosanoid generation by amplifying pivotal enzymatic events in lipoxygenase biosynthetic pathways and facilitating transfer of relatively unstable lipophilic lipoxygenase-derived intermediates 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 addition to the families of eicosanoids, inhibit LT-induced polymorphonuclear neutrophil (PMN) chemotaxis, adhesion to endothelial cells, diapedesis, vasoconstriction, and bronchoconstriction in several model systems and are potential modulators of LT bioactivity that may serve to limit PMN-mediated tissue injury in host defense, inflammation, ischemia-reperfusion, hemostasis, and other vascular events.
authors.affiliation: Renal Division, Medical Service, Brockton-West Roxbury Department of Veterans Affairs Medical Center, Boston, MA 02115 USA.; Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 USA.
authors.forename: H R
authors.initials: HR
authors.lastname: Brady
authors.forename: A
authors.initials: A
authors.lastname: Papayianni
authors.forename: C N
authors.initials: CN
authors.lastname: Serhan