Leukotriene B4 plays a pivotal role in CD40-dependent activation of chronic B lymphocytic leukemia cells.

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

Blood

journal_title

Blood

authors

Runarsson G,Liu A,Mahshid Y,Feltenmark S,Pettersson A,Klein E,Björkholm M,Claesson HE

doi

10.1182/blood-2004-07-2546

subject

Has Abstract

pub_date

2005-02-01 00:00:00

pages

1274-9

issue

3

eissn

0006-4971

issn

1528-0020

pii

2004-07-2546

journal_volume

105

pub_type

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