Rapid import of cytosolic 5-lipoxygenase into the nucleus of neutrophils after in vivo recruitment and in vitro adherence

被引:97
作者
Brock, TG
McNish, RW
Bailie, MB
PetersGolden, M
机构
[1] Div. Pulmon. and Critical Care Med., Department of Internal Medicine, University of Michigan, Ann Arbor
[2] M3317 Medical Sciences I, Div. Pulmon. and Critical Care Med., University of Michigan, Ann Arbor
关键词
D O I
10.1074/jbc.272.13.8276
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
5-Lipoxygenase catalyzes the synthesis of leukotrienes from arachidonic acid, The subcellular distribution of 5-lipoxygenase is known to be cell type dependent and is cytosolic in blood neutrophils. In this study, we asked whether neutrophil recruitment into sites of inflammation can alter the subcellular compartmentation of 5-lipoxygenase. In peripheral blood neutrophils from rats, 5-lipoxygenase was exclusively cytosolic, as expected, However, in glycogen-elicited peritoneal neutrophils, abundant soluble 5-lipoxygenase was in the nucleus, Upon activation with calcium ionophore A23187, intranuclear 5-lipoxygenase translocated to the nuclear envelope, Elicited neutrophils required a greater concentration of A23187 for activation than did blood neutrophils (half-maximal response, 160 versus 52 nM, respectively) but generated greater amounts of leukotriene B-4 upon maximal stimulation (26.6 versus 7.68 ng/10(6) cells, respectively), Intranuclear 5-lipoxygenase was also evident in human blood neutrophils after adherence to a variety of surfaces, suggesting that adherence alone is sufficient to drive 5-lipoxygenase redistribution, These results demonstrate a physiologically relevant circumstance in which the subcellular distribution of 5-lipoxygenase can be rapidly altered in resting cells, independent of 5-lipoxygenase activation, Nuclear import of 5-lipoxygenase may be a universal accompaniment of neutrophil recruitment into sites of inflammation, and this may be associated with alterations in enzymatic function.
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页码:8276 / 8280
页数:5
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