Hypoxia selectively inhibits respiratory burst activity and killing of Staphylococcus aureus in human neutrophils.
Hypoxia selectively inhibits respiratory burst activity and killing of Staphylococcus aureus in human neutrophils.
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DOI：
10.4049/jimmunol.1002213
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发表时间：
2011-01-01
期刊：
影响因子：
--
通讯作者：
Chilvers ER
中科院分区：
文献类型：
--
作者：
McGovern NN;Cowburn AS;Porter L;Walmsley SR;Summers C;Thompson AAR;Anwar S;Willcocks LC;Whyte MKB;Condliffe AM;Chilvers ER
中性粒细胞在先天免疫反应中发挥着核心作用，在杀灭细菌方面也发挥着关键作用。大多数中性粒细胞功能的研究都是在环境氧气条件下进行的，但中性粒细胞发挥作用的发炎部位可能极度缺氧。先前的研究表明，中性粒细胞通过普遍存在的脯氨酰羟化酶/缺氧诱导因子途径感知缺氧并做出反应，这可以发出增强生存的信号。在当前的研究中，人类中性粒细胞在低氧孵育条件（3 kPa）下上调缺氧诱导因子（HIF）-1α依赖性基因表达，从而显着延迟细胞凋亡的发生。尽管如此，对 IL-8 和 fMLP 的极化和趋化反应完全不受缺氧影响。同样，缺氧并没有减弱中性粒细胞吞噬血清调理热灭活链球菌的能力。在检查的分泌功能中，IL-8 的产生得以保留，弹性蛋白酶的释放因缺氧而增强。然而，缺氧确实导致由可溶性激动剂 fMLP 和摄入调理酵母聚糖诱导的呼吸爆发活性大幅降低，但不影响 NADPH 氧化酶亚基的表达。至关重要的是，缺氧条件下呼吸爆发活动的减少与杀死金黄色葡萄球菌的显着缺陷有关。相比之下，对大肠杆菌的杀灭作用主要是不依赖于氧化酶的，在缺氧条件下得到了完全保留。总之，这些研究表明，尽管缺氧可能会损害 NADPH 氧化酶依赖性细菌杀灭机制，但中性粒细胞总体上似乎非常适合在严重缺氧条件下成功运作。
Neutrophils play a central role in the innate immune response and a critical role in bacterial killing. Most studies of neutrophil function have been conducted under conditions of ambient oxygen, but inflamed sites where neutrophils operate may be extremely hypoxic. Previous studies indicate that neutrophils sense and respond to hypoxia via the ubiquitous prolyl hydroxylase/hypoxia-inducible factor pathway and that this can signal for enhanced survival. In the current study, human neutrophils were shown to upregulate hypoxia-inducible factor (HIF)-1α–dependent gene expression under hypoxic incubation conditions (3 kPa), with a consequent substantial delay in the onset of apoptosis. Despite this, polarization and chemotactic responsiveness to IL-8 and fMLP were entirely unaffected by hypoxia. Similarly, hypoxia did not diminish the ability of neutrophils to phagocytose serum-opsonized heat-killed streptococci. Of the secretory functions examined, IL-8 generation was preserved and elastase release was enhanced by hypoxia. Hypoxia did, however, cause a major reduction in respiratory burst activity induced both by the soluble agonist fMLP and by ingestion of opsonized zymosan, without affecting expression of the NADPH oxidase subunits. Critically, this reduction in respiratory burst activity under hypoxia was associated with a significant defect in the killing of Staphylococcus aureus. In contrast, killing of Escherichia coli, which is predominantly oxidase independent, was fully preserved under hypoxia. In conclusion, these studies suggest that although the NADPH oxidase-dependent bacterial killing mechanism may be compromised by hypoxia, neutrophils overall appear extremely well adapted to operate successfully under severely hypoxic conditions.
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DOI：
10.1073/pnas.0401339101
发表时间：
2004-07-13
影响因子：
11.1
作者：
Kong, TQ;Eltzschig, HK;Shelley, CS
通讯作者：
Shelley, CS
影响因子：
3.7
作者：
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通讯作者：
Anderson, BO
影响因子：
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作者：
INAUEN, W;GRANGER, DN;KVIETYS, PR
通讯作者：
KVIETYS, PR
影响因子：
64.5
作者：
Cramer, T;Yamanishi, Y;Johnson, RS
通讯作者：
Johnson, RS
影响因子：
1.5
作者：
AHN, ST;MUSTOE, TA
通讯作者：
MUSTOE, TA