Abstract
SEVERAL inflammatory diseases, including asthma, arthritis and psoriasis are associated with the production of leukotrienes by neutrophils, mast cells and macrophages1–3. The initial enzymatic step in the formation of leukotrienes is the oxidation of arachidonic acid by 5-lipoxygenase (5-LO) to leukotriene A4 (refs 4–6). Osteosarcoma cells transfected with 5-LO express active enzyme in broken cell preparations, but no leukotriene metabolites are produced by these cells when stimulated with the calcium ionophore A23187, indicating that an additional component is necessary for cellular 5-LO activity7. A new class of indole leukotriene inhibitor has been described that inhibits the formation of cellular leukotrienes but has no direct inhibitory effect on soluble 5-LO activity8. We have now used these potent agents to identify and isolate a novel membrane protein of relative molecular mass 18,000 which is necessary for cellular leukotriene synthesis.
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References
Samuelsson, B. Science 220, 568–575 (1983).
Samuelsson, B., Dahlen, S. E., Lindgren, J. A., Rouzer, C. A. & Serhan, C. N. Science 237, 1171–1176 (1987).
Rokach, J. Leukotrienes and Lipoxygenases (Elsevier, Amsterdam, 1989).
Shimizu, T., Radmark, O. & Samuelsson, B. Proc. natn. Acad. Sci. U.S.A. 81, 689–693 (1984).
Shimizu, T. et al. Proc. natn. Acad. Sci. U.S.A. 83, 4175–4179 (1986).
Rouzer, C. A., Matsumoto, T. & Samuelsson, B. Proc. natn. Acad. Sci. U.S.A. 83, 857–861 (1986).
Rouzer, C. A. et al. J. biol. Chem. 263, 10135–10140 (1988).
Gillard, J. et al. Can. J. Physiol. Pharmac. 67, 456–464 (1989).
Rouzer, C. A. J. biol. Chem. (in the press).
Rouzer, C. A. & Kargman, S. J. biol. Chem. 263, 10980–10988 (1988).
Kuehl, F. A. Jr., Dougherty, H. W. & Ham, E. A. Biochem. Pharmac. 33, 1–5 (1984).
Chilton, F. H. Biochem. J. 258, 327–333 (1989).
Ham, E. A. et al. Proc. natn. Acad. Sci. U.S.A. 80, 4349–4353 (1983).
Boyum, A. Scand. J. clin. Lab. Invest. (suppl. 97) 21, 77–89 (1968).
Guindon, Y. et al. in Advances in Prostaglandin, Thromboxane and Leukotriene Research (eds Samuelsson, B., Paoletti, R. & Ramwell, P. W.) 554–557 (Raven, New York, 1987).
Gan, Z. R. Gene 79, 159–166 (1989).
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Miller, D., Gillard, J., Vickers, P. et al. Identification and isolation of a membrane protein necessary for leukotriene production. Nature 343, 278–281 (1990). https://doi.org/10.1038/343278a0
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DOI: https://doi.org/10.1038/343278a0
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