Inhibition of spontaneous neutrophil apoptosis by parabutoporin acts independently of NADPH oxidase inhibition but by lipid raft-dependent stimulation of Akt
Inhibition of spontaneous neutrophil apoptosis by parabutoporin acts independently of NADPH oxidase inhibition but by lipid raft-dependent stimulation of Akt
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DOI：
10.1189/jlb.0908525
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发表时间：
2009-03-01
影响因子：
5.5
通讯作者：
Willems, Jean
中科院分区：
文献类型：
--
作者：
Remijsen, Quinten;Vanden Berghe, Tom;Willems, Jean
中性粒细胞死亡在中性粒细胞稳态和炎症消退中起着至关重要的作用。产生超氧化物的NADPH氧化酶参与病原体降解和随后的细胞死亡程序的激活。NADPH氧化酶活性不足的慢性肉芽肿患者的中性粒细胞先前已被证明具有较长的寿命，这表明基础NADPH氧化酶活性也调节自发性中性粒细胞周转。NADPH氧化酶抑制剂parabutoporin （PP）确实可以延缓细胞自发凋亡，但这种作用完全独立于NADPH氧化酶抑制。相反，PP的促存活作用取决于通过脂质筏信号激活蛋白激酶B/Akt。脂筏的破坏在不干扰NADPH氧化酶活性的情况下消除了促生存作用。此外，我们无法在正常和缺乏NADPH氧化酶的中性粒细胞之间检测到不同的自发凋亡率，从而反驳了NADPH氧化酶在中性粒细胞自发凋亡中的作用。j . Leukoc。生物学报。85:497-507；2009.
Neutrophil cell death plays a crucial role in neutrophil homeostasis and the resolution of inflammation. The superoxide-producing NADPH oxidase is involved in pathogen degradation and subsequent activation of cell death programs. Neutrophils from patients with chronic granulomatous disease, who have a deficient NADPH oxidase activity, have been demonstrated previously to have a prolonged lifespan, suggesting that a basal NADPH oxidase activity also regulates spontaneous neutrophil turnover. The NADPH oxidase inhibitor parabutoporin (PP) does delay spontaneous apoptosis, but this effect is completely independent of NADPH oxidase inhibition. Instead, the prosurvival effect of PP depends on activation of protein kinase B/Akt via lipid raft signaling. Disruption of lipid rafts abrogates the prosurvival effect without interfering with NADPH oxidase activity. Furthermore, we cannot detect a different rate of spontaneous apoptosis between normal and NADPH oxidase-deficient neutrophils, arguing against a role of NADPH oxidase in spontaneous neutrophil apoptosis. J. Leukoc. Biol. 85: 497-507; 2009.