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The effects of neutrophil-generated hypochlorous acid and other hypohalous acids on host and pathogens.
Cellular and Molecular Life Sciences ( IF 8 ) Pub Date : 2020-07-13 , DOI: 10.1007/s00018-020-03591-y
Agnes Ulfig 1 , Lars I Leichert 1
Affiliation  

Neutrophils are predominant immune cells that protect the human body against infections by deploying sophisticated antimicrobial strategies including phagocytosis of bacteria and neutrophil extracellular trap (NET) formation. Here, we provide an overview of the mechanisms by which neutrophils kill exogenous pathogens before we focus on one particular weapon in their arsenal: the generation of the oxidizing hypohalous acids HOCl, HOBr and HOSCN during the so-called oxidative burst by the enzyme myeloperoxidase. We look at the effects of these hypohalous acids on biological systems in general and proteins in particular and turn our attention to bacterial strategies to survive HOCl stress. HOCl is a strong inducer of protein aggregation, which bacteria can counteract by chaperone-like holdases that bind unfolding proteins without the need for energy in the form of ATP. These chaperones are activated by HOCl through thiol oxidation (Hsp33) or N-chlorination of basic amino acid side-chains (RidA and CnoX) and contribute to bacterial survival during HOCl stress. However, neutrophil-generated hypohalous acids also affect the host system. Recent studies have shown that plasma proteins act not only as sinks for HOCl, but get actively transformed into modulators of the cellular immune response through N-chlorination. N-chlorinated serum albumin can prevent aggregation of proteins, stimulate immune cells, and act as a pro-survival factor for immune cells in the presence of cytotoxic antigens. Finally, we take a look at the emerging role of HOCl as a potential signaling molecule, particularly its role in neutrophil extracellular trap formation.



中文翻译:

中性粒细胞产生的次氯酸和其他次卤酸对宿主和病原体的影响。

中性粒细胞是主要的免疫细胞,通过部署复杂的抗菌策略(包括吞噬细菌和中性粒细胞胞外陷阱(NET)形成)来保护人体免受感染。在这里,我们概述了中性粒细胞杀死外源性病原体的机制,然后我们关注中性粒细胞武器库中的一种特殊武器:在髓过氧化物酶的所谓氧化爆发过程中产生氧化性次卤酸 HOCl、HOBr 和 HOSCN。我们研究了这些次卤酸对生物系统的影响,特别是对蛋白质的影响,并将我们的注意力转向细菌在次卤酸胁迫下生存的策略。HOCl 是蛋白质聚集的强诱导剂,细菌可以通过类似分子伴侣的保持酶来抵消这种聚集,这些保持酶结合未折叠的蛋白质,而不需要 ATP 形式的能量。这些分子伴侣通过硫醇氧化 (Hsp33) 或碱性氨基酸侧链(RidA 和 CnoX)的 N-氯化被 HOCl 激活,并有助于细菌在 HOCl 胁迫期间存活。然而,中性粒细胞产生的次卤酸也会影响宿主系统。最近的研究表明,血浆蛋白不仅充当 HOCl 的接收器,而且还通过 N-氯化主动转化为细胞免疫反应的调节剂。N-氯化血清白蛋白可以防止蛋白质聚集,刺激免疫细胞,并在细胞毒性抗原存在的情况下充当免疫细胞的促生存因子。最后,我们研究了次氯酸作为潜在信号分子的新作用,特别是它在中性粒细胞胞外陷阱形成中的作用。

更新日期:2020-07-13
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