Abstract:
:Biosynthesis 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 LTB(4) (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 LTB(4) (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.
journal_name
Bloodjournal_title
Bloodauthors
Runarsson G,Liu A,Mahshid Y,Feltenmark S,Pettersson A,Klein E,Björkholm M,Claesson HEdoi
10.1182/blood-2004-07-2546subject
Has Abstractpub_date
2005-02-01 00:00:00pages
1274-9issue
3eissn
0006-4971issn
1528-0020pii
2004-07-2546journal_volume
105pub_type
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