NADPH-oxidase activation in murine neutrophils via formyl peptide receptors

NADPH-oxidase activation in murine neutrophils via formyl peptide receptors
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DOI:
10.1016/s0014-4827(02)00010-1
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发表时间:
2003-01-15
影响因子:
3.7
通讯作者:
Karlsson, A
Karlsson, A
中科院分区:
医学3区
文献类型:
--
作者:
Bylund, J;Samuelsson, M;Karlsson, A

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中性粒细胞在炎症部位起关键作用,除了破坏感染微生物外,它们还可能对宿主组织产生有害影响。这两种活性都涉及NADPH氧化酶的激活,产生杀菌和组织破坏性活性氧(ROS)。我们使用不同类型的中性粒细胞激活剂激活小鼠NADPH氧化酶,并从幅度、定位和动力学方面表征氧化反应。我们发现,激动剂诱导的激活常规中性粒细胞的结果只在细胞外释放的活性氧和没有细胞内的生产可以检测到。我们还表明,甲酰化的肽,甲酰-蛋氨酸-亮氨酸-苯丙氨酸(fMLF),是一个更有效的激活剂的小鼠NADPH氧化酶比人类类似物。然而,fMLF反应可以通过用细胞松弛素B或细菌脂多糖预处理鼠嗜中性粒细胞来引发。最后,我们表明,合成的六肽,WKYMVM,是一个更有力的刺激比fMLF小鼠中性粒细胞,这两个激动剂可能通过不同的高亲和力受体的行为。(C)2003 Elsevier Science(美国)。All rights reserved.
Neutrophils play a key role at inflammatory sites where, in addition to destroying infecting microorganisms, they may also have deleterious effects on host tissues. Both activities involve activation of the NADPH-oxidase that produces bactericidal and tissue-destructive reactive oxygen species (ROS). We activated the murine NADPH-oxidase using different types of neutrophil activators and characterized the oxidative responses with respect to magnitude, localization, and kinetics. We show that agonist-induced activation of routine neutrophils results exclusively in extracellular release of ROS and no intracellular production could be detected. We also show that the formylated peptide, formyl-Met-Leu-Phe (fMLF), is a much less potent activator of the murine NADPH-oxidase than of the human analogue. Nevertheless, fMLF responses can be primed by pretreating the murine neutrophils with either cytochalasin B or bacterial lipopolysaccharide. Finally, we show that a synthetic hexapeptide, WKYMVM, is a more potent stimulus than fMLF for murine neutrophils and that these two agonists probably act via nonidentical high-affinity receptors. (C) 2003 Elsevier Science (USA). All rights reserved.