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Leukotriene B-4 plays a pivotal role in CD40-dependent activation of chronic B lymphocytic leukemia cells

Runarsson, G; Liu, AQ; Mahshid, Y; Feltenmark, S; Pettersson, Annika LU ; Klein, E; Bjorkholm, M and Claesson, HE (2005) In Blood 105(3). p.1274-1279
Abstract
Blosynthesis of leukotrienes (LTs) 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 B-4, 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. At a concentration of 100 nM, the drugs BWA4C (a specific 5-lipoxygenase inhibitor) and MK-886 (a specific 5-lipoxygenase activating protein inhibitor) markedly inhibited CD40-induced DNA synthesis... (More)
Blosynthesis of leukotrienes (LTs) 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 B-4, 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. At a concentration of 100 nM, the drugs BWA4C (a specific 5-lipoxygenase inhibitor) and MK-886 (a specific 5-lipoxygenase activating protein inhibitor) 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood
volume
105
issue
3
pages
1274 - 1279
publisher
American Society of Hematology
external identifiers
  • pmid:15454480
  • wos:000226596700059
  • scopus:12844258796
ISSN
1528-0020
DOI
10.1182/blood-2004-07-2546
language
English
LU publication?
yes
id
2e01a9ca-ecc8-428f-9e35-57c7d7f4afc6 (old id 254962)
date added to LUP
2007-08-16 16:00:35
date last changed
2017-08-27 04:05:38
@article{2e01a9ca-ecc8-428f-9e35-57c7d7f4afc6,
  abstract     = {Blosynthesis of leukotrienes (LTs) 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 B-4, 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. At a concentration of 100 nM, the drugs BWA4C (a specific 5-lipoxygenase inhibitor) and MK-886 (a specific 5-lipoxygenase activating protein inhibitor) 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.},
  author       = {Runarsson, G and Liu, AQ and Mahshid, Y and Feltenmark, S and Pettersson, Annika and Klein, E and Bjorkholm, M and Claesson, HE},
  issn         = {1528-0020},
  language     = {eng},
  number       = {3},
  pages        = {1274--1279},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Leukotriene B-4 plays a pivotal role in CD40-dependent activation of chronic B lymphocytic leukemia cells},
  url          = {http://dx.doi.org/10.1182/blood-2004-07-2546},
  volume       = {105},
  year         = {2005},
}