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Blood, 1 February 2005, Vol. 105, No. 3, pp. 1274-1279. Prepublished online as a Blood First Edition Paper on September 28, 2004; DOI 10.1182/blood-2004-07-2546. This Article Full Text (PDF) All Versions of this Article: 2004-07-2546v1 105/3/1274    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Runarsson, G. Articles by Claesson, H.-E. Search for Related Content PubMed PubMed Citation Articles by Runarsson, G. Articles by Claesson, H.-E. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 7, 2004 Accepted September 16, 2004 Leukotriene B4 plays a pivotal role in CD40 dependent activation of chronic B lymphocytic leukemia cells Gudmundur Runarsson, Anquan Liu, Yilmaz Mahshid, Stina Feltenmark, Annika Pettersson, Eva Klein, Magnus Bjorkholm, and Hans-Erik Claesson* Department of Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden Microbiology and Tumour Biology Center, Karolinska Institutet, Stockholm, Sweden Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden Division of Molecular Neurobiology, Wallenberg Neuroscience Center, Lund University, Lund, Sweden Department of Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden * Corresponding author; email: hans-erik.claesson{at}mbb.ki.se. Biosynthesis of leukotrienes occurs in human myeloid cells and B lymphocytes. However, the function of leukotrienes in B lymphocytes is unclear. Here we report that B-cell chronic lymphocytic leukemia (B-CLL) cells produce leukotriene (LT) B4 and that specific leukotriene biosynthesis inhibitors counteracted CD40-dependent activation of B-CLL cells. Studies on the expression of the high affinity receptor for LTB4 (BLT1) by flow cytometry analysis showed that the receptor was expressed, to a varying degree, in all investigated B-CLL clones. The drugs BWA4C (a specific 5-lipoxygenase inhibitor) and MK-886 (a specific 5-lipoxygenase activating protein inhibitor), at a concentration of 100 nM, markedly inhibited CD40-induced DNA synthesis (45% and 38%, respectively) and CD40-induced expression of CD23, CD54 and CD150. Addition of exogenous LTB4 (150 nM) almost completely reversed the effect of the inhibitors on DNA synthesis and antigen expression. Taken together, the results of the present study suggest that leukotriene biosynthesis inhibitors may have a therapeutic role in B-CLL. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Buchner, S. Fuchs, G. Prinz, D. Pfeifer, K. Bartholome, M. Burger, N. Chevalier, L. Vallat, J. Timmer, J. G. Gribben, et al. Spleen Tyrosine Kinase Is Overexpressed and Represents a Potential Therapeutic Target in Chronic Lymphocytic Leukemia Cancer Res., July 1, 2009; 69(13): 5424 - 5432. [Abstract] [Full Text] [PDF] A. Liu, H.-E. Claesson, Y. Mahshid, G. Klein, and E. Klein Leukotriene B4 activates T cells that inhibit B-cell proliferation in EBV-infected cord blood-derived mononuclear cell cultures Blood, March 1, 2008; 111(5): 2693 - 2703. [Abstract] [Full Text] [PDF] M. Peters-Golden and W. R. Henderson Jr. Leukotrienes N. Engl. J. Med., November 1, 2007; 357(18): 1841 - 1854. [Full Text] [PDF] M. Arguello, S. Paz, E. Hernandez, C. Corriveau-Bourque, L. M. Fawaz, J. Hiscott, and R. Lin Leukotriene A4 Hydrolase Expression in PEL Cells Is Regulated at the Transcriptional Level and Leads to Increased Leukotriene B4 Production. J. Immunol., June 1, 2006; 176(11): 7051 - 7061. [Abstract] [Full Text] [PDF] D. de Totero, R. Meazza, S. Zupo, G. Cutrona, S. Matis, M. Colombo, E. Balleari, I. Pierri, M. Fabbi, M. Capaia, et al. Interleukin-21 receptor (IL-21R) is up-regulated by CD40 triggering and mediates proapoptotic signals in chronic lymphocytic leukemia B cells Blood, May 1, 2006; 107(9): 3708 - 3715. [Abstract] [Full Text] [PDF] A. L. Mayburd, A. Martlinez, D. Sackett, H. Liu, J. Shih, J. Tauler, I. Avis, and J. L. Mulshine Ingenuity Network-Assisted Transcription Profiling: Identification of a New Pharmacologic Mechanism for MK886. Clin. Cancer Res., March 15, 2006; 12(6): 1820 - 1827. [Abstract] [Full Text] [PDF]

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