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Science 4 September 1987:
Vol. 237. no. 4819, pp. 1171 - 1176
DOI: 10.1126/science.2820055
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Articles

Science, Vol 237, Issue 4819, 1171-1176
Copyright © 1987 by American Association for the Advancement of Science

articles

Leukotrienes and lipoxins: structures, biosynthesis, and biological effects

B Samuelsson, SE Dahlen, JA Lindgren, CA Rouzer, and CN Serhan

Arachidonic acid is released from membrane phospholipids upon cell stimulation (for example, by immune complexes and calcium ionophores) and converted to leukotrienes by a 5-lipoxygenase that also has leukotriene A4 synthetase activity. Leukotriene A4, an unstable epoxide, is hydrolyzed to leukotriene B4 or conjugated with glutathione to yield leukotriene C4 and its metabolites, leukotriene D4 and leukotriene E4. The leukotrienes participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. Recent studies also suggest a neuroendocrine role for leukotriene C4 in luteinizing hormone secretion. Lipoxins are formed by the action of 5- and 15-lipoxygenases on arachidonic acid. Lipoxin A causes contraction of guinea pig lung strips and dilation of the microvasculature. Both lipoxin A and B inhibit natural killer cell cytotoxicity. Thus, the multiple interaction of lipoxygenases generates compounds that can regulate specific cellular responses of importance in inflammation and immunity.


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Am. J. Respir. Crit. Care Med. 169, 407-412
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Role of Leukotriene B4 Receptors in the Development of Atherosclerosis: Potential Mechanisms.
K. Subbarao, V. R. Jala, S. Mathis, J. Suttles, W. Zacharias, J. Ahamed, H. Ali, M. T. Tseng, and B. Haribabu (2004)
Arterioscler Thromb Vasc Biol 24, 369-375
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Arachidonate 5-Lipoxygenase Promoter Genotype, Dietary Arachidonic Acid, and Atherosclerosis.
J. H. Dwyer, H. Allayee, K. M. Dwyer, J. Fan, H. Wu, R. Mar, A. J. Lusis, and M. Mehrabian (2004)
N. Engl. J. Med. 350, 29-37
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A Scorpion Venom Peptide Fraction Induced Prostaglandin Biosynthesis in Guinea Pig Kidneys: Incorporation of 14C-Linoleic Acid.
M. A. El-Saadani (2004)
J. Biochem. 135, 109-116
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Reduced Inflammation and Tissue Damage in Transgenic Rabbits Overexpressing 15-Lipoxygenase and Endogenous Anti-inflammatory Lipid Mediators.
C. N. Serhan, A. Jain, S. Marleau, C. Clish, A. Kantarci, B. Behbehani, S. P. Colgan, G. L. Stahl, A. Merched, N. A. Petasis, et al. (2003)
J. Immunol. 171, 6856-6865
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Bronchial Mast Cells Are the Dominating LTC4S-Expressing Cells in Aspirin-Tolerant Asthma.
Y. Cai, L. Bjermer, and T. S. Halstensen (2003)
Am. J. Respir. Cell Mol. Biol. 29, 683-693
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The C2-like {beta}-Barrel Domain Mediates the Ca2+-dependent Resistance of 5-Lipoxygenase Activity Against Inhibition by Glutathione Peroxidase-1.
E. Burkert, C. Arnold, T. Hammarberg, O. Radmark, D. Steinhilber, and O. Werz (2003)
J. Biol. Chem. 278, 42846-42853
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Helix 8 of the Leukotriene B4 Receptor Is Required for the Conformational Change to the Low Affinity State after G-protein Activation.
T. Okuno, H. Ago, K. Terawaki, M. Miyano, T. Shimizu, and T. Yokomizo (2003)
J. Biol. Chem. 278, 41500-41509
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Differential Leukotriene Receptor Expression and Calcium Responses in Endothelial Cells and Macrophages Indicate 5-Lipoxygenase-Dependent Circuits of Inflammation and Atherogenesis.
K. Lotzer, R. Spanbroek, M. Hildner, A. Urbach, R. Heller, E. Bretschneider, H. Galczenski, J. F. Evans, and A. J.R. Habenicht (2003)
Arterioscler Thromb Vasc Biol 23, e32-36
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Success of prostaglandin E2 in structure-function is a challenge for structure-based therapeutics.
C. N. Serhan and B. Levy (2003)
PNAS 100, 8609-8611
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Platelet-activating Factor-mediated NF-{kappa}B Dependency of a Late Anaphylactic Reaction.
I.-W. Choi, Y.-S. Kim, D.-K. Kim, J.-H. Choi, K.-H. Seo, S.-Y. Im, K.-S. Kwon, M.-S. Lee, T.-Y. Ha, and H.-K. Lee (2003)
J. Exp. Med. 198, 145-151
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Amino Acid Differences in the Deduced 5-Lipoxygenase Sequence of CAST Atherosclerosis-Resistance Mice Confer Impaired Activity When Introduced Into the Human Ortholog.
H. Kuhn, M. Anton, C. Gerth, and A. Habenicht (2003)
Arterioscler Thromb Vasc Biol 23, 1072-1076
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Novel Docosatrienes and 17S-Resolvins Generated from Docosahexaenoic Acid in Murine Brain, Human Blood, and Glial Cells. AUTACOIDS IN ANTI-INFLAMMATION.
S. Hong, K. Gronert, P. R. Devchand, R.-L. Moussignac, and C. N. Serhan (2003)
J. Biol. Chem. 278, 14677-14687
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5-Lipoxygenase-activating Protein Gene Expression. KEY ROLE OF CCAAT/ENHANCER-BINDING PROTEINS (C/EBP) IN CONSTITUTIVE AND TUMOR NECROSIS FACTOR (TNF) alpha -INDUCED EXPRESSION IN THP-1 CELLS.
K. V. Reddy, K. J. Serio, C. R. Hodulik, and T. D. Bigby (2003)
J. Biol. Chem. 278, 13810-13818
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Lipoxin A4 Stimulates a Cytosolic Ca2+ Increase in Human Bronchial Epithelium.
C. Bonnans, B. Mainprice, P. Chanez, J. Bousquet, and V. Urbach (2003)
J. Biol. Chem. 278, 10879-10884
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International Union of Pharmacology XXXVII. Nomenclature for Leukotriene and Lipoxin Receptors.
C. Brink, S.-E. Dahlen, J. Drazen, J. F. Evans, D. W. P. Hay, S. Nicosia, C. N. Serhan, T. Shimizu, and T. Yokomizo (2003)
Pharmacol. Rev. 55, 195-227
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Expanding expression of the 5-lipoxygenase pathway within the arterial wall during human atherogenesis.
R. Spanbroek, R. Grabner, K. Lotzer, M. Hildner, A. Urbach, K. Ruhling, M. P. W. Moos, B. Kaiser, T. U. Cohnert, T. Wahlers, et al. (2003)
PNAS 100, 1238-1243
   Abstract »    Full Text »    PDF »
Resolution of Inflammation: A New Paradigm for the Pathogenesis of Periodontal Diseases.
T. E. Van Dyke and C.N. Serhan (2003)
Journal of Dental Research 82, 82-90
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Modulation of Aspirin-Insensitive Eicosanoid Biosynthesis by 6-Methylprednisolone in Unstable Angina.
F. Cipollone, A. Ganci, A. Greco, M. R. Panara, M. Pasquale, D. Di Gregorio, E. Porreca, A. Mezzetti, F. Cuccurullo, and P. Patrignani (2003)
Circulation 107, 55-61
   Abstract »    Full Text »    PDF »
LIPOXINS IN CHRONIC INFLAMMATION.
A. Kantarci and T. E. Van Dyke (2003)
Critical Reviews in Oral Biology & Medicine 14, 4-12
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Prostaglandins Inhibit 5-Lipoxygenase-Activating Protein Expression and Leukotriene B4 Production from Dendritic Cells Via an IL-10-Dependent Mechanism.
H. Harizi, M. Juzan, J.-F. Moreau, and N. Gualde (2003)
J. Immunol. 170, 139-146
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