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Related Collections Phagocytes Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 April 2001, Vol. 97, No. 8, pp. 2487-2495 PHAGOCYTES Phorbol ester up-regulates capacities for nuclear translocation and phosphorylation of 5-lipoxygenase in Mono Mac 6 cells and human polymorphonuclear leukocytes Oliver Werz, Jenny Klemm, Bengt Samuelsson, and Olof Rådmark From the Department of Medical Biochemistry and Biophysics, Division of Physiological Chemistry II, Karolinska Institutet, Stockholm, Sweden. The leukotrienes are inflammatory mediators derived from arachidonic acid. It was demonstrated that the priming of leukocytes with phorbol-12-myristate-13-acetate (PMA) leads to the increased formation of 5-lipoxygenase (5-LO) products in parallel with the increased association of 5-LO with the nucleus and the activation of kinases that can phosphorylate 5-LO in vitro. Stimulation of the monocytic cell line Mono Mac 6 with calcium ionophore gave low 5-LO product formation and no detectable redistribution of 5-LO. However, after priming of Mono Mac 6 cells with phorbol esters, ionophore led to the association of 45% to 75% of cellular 5-LO with the nuclear membrane, to 5-LO kinase activation, to enhanced release of arachidonate, and to substantial leukotriene synthesis. Similar results were obtained for human polymorphonuclear leukocytes stimulated with low-dose ionophore. In addition, for each cell type, PMA priming up-regulated leukotriene biosynthesis in the presence of exogenous arachidonic acid. A protein kinase inhibitor, calphostin C, reduced the association of 5-LO with the nucleus and 5-LO kinase activity, and the formation of 5-LO products was inhibited. These results suggest that PMA up-regulates leukotriene biosynthesis not only by increasing the release of endogenous arachidonate, but also by increasing the capacity for 5-LO phosphorylation and for the translocation of 5-LO to the nucleus in leukocytes. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. C. Lindner, U. Kohl, T. J. Maier, D. Steinhilber, and B. L. Sorg TLR2 ligands augment cPLA2{alpha} activity and lead to enhanced leukotriene release in human monocytes J. Leukoc. Biol., August 1, 2009; 86(2): 389 - 399. [Abstract] [Full Text] [PDF] C. Pergola, G. Dodt, A. Rossi, E. Neunhoeffer, B. Lawrenz, H. Northoff, B. Samuelsson, O. Radmark, L. Sautebin, and O. Werz ERK-mediated regulation of leukotriene biosynthesis by androgens: A molecular basis for gender differences in inflammation and asthma PNAS, December 16, 2008; 105(50): 19881 - 19886. [Abstract] [Full Text] [PDF] D. Albert, C. Pergola, A. Koeberle, G. Dodt, D. Steinhilber, and O. Werz The role of diacylglyceride generation by phospholipase D and phosphatidic acid phosphatase in the activation of 5-lipoxygenase in polymorphonuclear leukocytes J. Leukoc. Biol., April 1, 2008; 83(4): 1019 - 1027. [Abstract] [Full Text] [PDF] M. Rakonjac, L. Fischer, P. Provost, O. Werz, D. Steinhilber, B. Samuelsson, and O. Radmark Coactosin-like protein supports 5-lipoxygenase enzyme activity and up-regulates leukotriene A4 production PNAS, August 29, 2006; 103(35): 13150 - 13155. [Abstract] [Full Text] [PDF] N. Flamand, J. Lefebvre, M. E. Surette, S. Picard, and P. Borgeat Arachidonic Acid Regulates the Translocation of 5-Lipoxygenase to the Nuclear Membranes in Human Neutrophils J. Biol. Chem., January 6, 2006; 281(1): 129 - 136. [Abstract] [Full Text] [PDF] C. Hornig, D. Albert, L. Fischer, M. Hornig, O. Radmark, D. Steinhilber, and O. Werz 1-Oleoyl-2-acetylglycerol Stimulates 5-Lipoxygenase Activity via a Putative (Phospho)lipid Binding Site within the N-terminal C2-like Domain J. Biol. Chem., July 22, 2005; 280(29): 26913 - 26921. [Abstract] [Full Text] [PDF] M. Luo, S. M. Jones, S. M. Phare, M. J. Coffey, M. Peters-Golden, and T. G. Brock Protein Kinase A Inhibits Leukotriene Synthesis by Phosphorylation of 5-Lipoxygenase on Serine 523 J. Biol. Chem., October 1, 2004; 279(40): 41512 - 41520. [Abstract] [Full Text] [PDF] M. Luo, S. M. Jones, M. Peters-Golden, and T. G. Brock Nuclear localization of 5-lipoxygenase as a determinant of leukotriene B4 synthetic capacity PNAS, October 14, 2003; 100(21): 12165 - 12170. [Abstract] [Full Text] [PDF] E. Burkert, D. Szellas, O. Radmark, D. Steinhilber, and O. Werz Cell type-dependent activation of 5-lipoxygenase by arachidonic acid J. Leukoc. Biol., January 1, 2003; 73(1): 191 - 200. [Abstract] [Full Text] [PDF] S. M. Jones, M. Luo, A. M. Healy, M. Peters-Golden, and T. G. Brock Structural and Functional Criteria Reveal a New Nuclear Import Sequence on the 5-Lipoxygenase Protein J. Biol. Chem., October 4, 2002; 277(41): 38550 - 38556. [Abstract] [Full Text] [PDF] N. Flamand, M. E. Surette, S. Picard, S. Bourgoin, and P. Borgeat Cyclic AMP-Mediated Inhibition of 5-Lipoxygenase Translocation and Leukotriene Biosynthesis in Human Neutrophils Mol. Pharmacol., August 1, 2002; 62(2): 250 - 256. [Abstract] [Full Text] [PDF] O. Werz, D. Szellas, D. Steinhilber, and O. Radmark Arachidonic Acid Promotes Phosphorylation of 5-Lipoxygenase at Ser-271 by MAPK-activated Protein Kinase 2 (MK2) J. Biol. Chem., April 19, 2002; 277(17): 14793 - 14800. [Abstract] [Full Text] [PDF] E. Burkert, O. Radmark, B. Samuelsson, D. Steinhilber, and O. Werz Hypertonicity suppresses ionophore-induced product formation and translocation of 5-lipoxygenase in human leukocytes J. Leukoc. Biol., March 1, 2002; 71(3): 477 - 486. [Abstract] [Full Text] [PDF] O. Werz, E. Burkert, B. Samuelsson, O. Radmark, and D. Steinhilber Activation of 5-lipoxygenase by cell stress is calcium independent in human polymorphonuclear leukocytes Blood, February 1, 2002; 99(3): 1044 - 1052. [Abstract] [Full Text] [PDF] O. Werz, J. Klemm, O. Radmark, and B. Samuelsson p38 MAP kinase mediates stress-induced leukotriene synthesis in a human B-lymphocyte cell line J. Leukoc. Biol., November 1, 2001; 70(5): 830 - 838. [Abstract] [Full Text] [PDF]

	Copyright © 2001 by American Society of Hematology         Online ISSN: 1528-0020