Priming of the neutrophil respiratory burst involves p38 mitogen-activated protein kinase-dependent exocytosis of flavocytochrome b558-containing granules

被引:137
作者
Ward, RA
Nakamura, M
McLeish, KR
机构
[1] Univ Louisville, Dept Med, Mol Signaling Grp, Louisville, KY 40202 USA
[2] Univ Louisville, Dept Biochem & Mol Biol, Louisville, KY 40202 USA
[3] Nagasaki Univ, Inst Trop Med, Dept Host Def Biochem, Nagasaki 8528523, Japan
[4] Vet Affairs Med Ctr, Louisville, KY 40204 USA
关键词
D O I
10.1074/jbc.M003017200
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
The respiratory burst of human neutrophils is primed by a number of pro-inflammatory stimuli, including tumor necrosis factor-alpha (TNF alpha) and lipopolysaccharide (LPS); however, the mechanism of priming remains unknown. LPS has been shown previously to increase membrane expression of flavocytochrome b(558), a component of the NADPH oxidase. This study shows that TNF alpha also increases membrane expression of flavocytochrome b(558). Mitogen-activated protein kinase (MAPK) modules have been implicated in the action of priming agents. Pharmacologic inhibitors of MAPKs, SB203580 and PD098059, revealed that priming of the respiratory burst and up-regulation of flavocytochrome b(558) are dependent on p38 MAPK but not on extracellular-signal regulated kinase (ERK). TNF alpha and LPS primed respiratory burst activity and increased membrane expression of CD35 and CD66b, specific markers of secretory vesicles and specific granules that contain flavocytochrome b(558) with similar time courses and concentration dependences. These processes also required p38 MAPK but were independent of ERK. TNF alpha failed to prime respiratory burst activity or to increase membrane CD35 expression in enucleated neutrophil cytoplasts. These data suggest that one mechanism by which TNF alpha and LPS prime neutrophil respiratory burst activity is by increasing membrane expression of flavocytochrome b(558) through exocytosis of intracellular granules in a process regulated by p38 MAPK.
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页码:36713 / 36719
页数:7
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