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Leukotrienes (LTs) are a group of acute inflammatory mediators derived from arachidonic acid in leukocytes. The majority of these metabolites are formed through the 5-lipoxygenase (5-LO) pathway.1 14,15-LTC4 is a member of an alternate class of LTs synthesized by a pathway involving the dual actions of 15- and 12-LOs on arachidonic acid via 15-HpETE and 14,15-LTA4 intermediates.2,3,4,5 14,15-LTC4 is classified as an eoxin, because it is formed mostly by eosinophils.4 However, mast cells and nasal polyps can synthesize 14,15-LTC4 as well. Little is known about the physiological actions of 14,15-LTC4. It has weak contractile activity on both guinea pig ileum and pulmonary parenchyma in contrast to the effects of 5-LO-derived LTs.6,7 However, in an in vitro permeability assay, 14,15-LTC4 can increase vascular permeability of human endothelial cell monolayers, with similar potency to that of 5-LO-derived LTs resulting in plasma leakage - a hallmark of inflammation.4
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1
Luo, M., Lee, S., Brock, T.G. Leukotriene synthesis by epithelial cells. Histol Histopathol 18 587-595 (2003).
2
Yokoyama, C., Shinjo, F., Yoshimoto, T., et al. Arachidonate 12-lipoxygenase purified from porcine leukocytes by immunoaffinity chromatography and its reactivity with hydroperoxyeicosatetraenoic acids. J Biol Chem 261 16714-16721 (1986).
3
Bryant, R.W., Schewe, T., Rapoport, S.M., et al. Leukotriene formation by a purified reticulocyte lipoxygenase enzyme. Conversion of arachidonic acid and 15-hydroperoxyeicosatetraenoic acid to 14,15-leukotriene A4. J Biol Chem 260 3548-3555 (1985).
4
Feltenmark, S., Gautam, N., Brunnström, Å., et al. Eoxins are proinflammatory arachidonic acid metabolites produced via the 15-lipoxygenase-1 pathway in human eosinophils and mast cells. Proc Natl Acad Sci USA 105(2) 680-685 (2008).
5
Sailesh, S., Kumar, Y.V.K., Prasad, M., et al. Sheep uterus dual lipoxygenase in the synthesis of 14,15-leukotrienes. Arch Biochem Biophys 315(2) 362-368 (1994).
6
Drazen, J.M., Lewis, R.A., Austen, K.F., et al. Contractile activities of structural analogs of leukotrienes C and D: Necessity of a hydrophobic region. Proc Natl Acad Sci USA 78(5) 3195-3198 (1987).
7
Sala, A., Civelli, M., Oliva, D., et al. Contractile and binding activities of structural analogues of LTC4 in the longitudinal muscle of guinea-pig ileum. Eicosanoids 3 105-110 (1990).
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