Taurine chloramine selectively regulates neutrophil degranulation through the inhibition of myeloperoxidase and upregulation of lactoferrin
Taurine chloramine selectively regulates neutrophil degranulation through the inhibition of myeloperoxidase and upregulation of lactoferrin
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DOI：
10.1007/s00726-020-02886-5
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发表时间：
2020-08-31
期刊：
影响因子：
3.5
通讯作者：
Kim, Chaekyun
中科院分区：
文献类型：
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作者：
Kim, Dong Gye;Kwon, Young Min;Kim, Chaekyun
牛磺酸是一种富含中性粒细胞的游离氨基酸，中性粒细胞在抵抗感染的前线发挥着重要作用。中性粒细胞激活后，牛磺酸与髓过氧化物酶（MPO）系统产生的次氯酸（HOCl/OCl-）反应，转化为牛磺酸氯胺（Tau-Cl）。中性粒细胞有三种类型的颗粒，其中初级颗粒MPO、二级颗粒乳铁蛋白和三级颗粒基质金属蛋白酶(MMP)-9通过脱粒过程释放到细胞外空间。MPO产生次氯酸来杀死微生物，释放的MPO与释放的染色质形成中性粒细胞胞外陷阱（NETs）。过量分泌MPO会对周围组织造成氧化损伤。乳铁蛋白发挥抗氧化活性，防止促炎途径激活、败血症和组织损伤，并延缓中性粒细胞凋亡。实验结果表明，中性粒细胞在失活状态下释放少量颗粒，12-肉豆肉酸13-乙酸酯（PMA）和n -甲酰基蛋氨酸-亮基苯丙氨酸可诱导中性粒细胞脱粒。Tau-Cl抑制pma诱导的MPO脱颗粒和NETs的形成。Tau-Cl能促进乳铁蛋白的脱粒，但对MMP-9的脱粒无影响。MPO负向调节巨噬细胞炎症蛋白(MIP)-2的产生，从而刺激中性粒细胞的脱粒和迁移。Tau-Cl可抑制MIP-2的表达，提示其对MPO释放的抑制作用。细胞内MPO水平的升高可能负向调控MIP-2的表达，从而进一步调控中性粒细胞的脱粒和迁移。在这里，我们建议Tau-Cl选择性地抑制MPO脱粒，并刺激中性粒细胞的乳铁蛋白脱粒，从而保护炎症组织免受过度释放MPO引起的氧化损伤。
Taurine is a free amino acid rich in neutrophils, and neutrophils play an important role in the forefront defense against infection. Upon neutrophil activation, taurine reacts with hypochlorous acid (HOCl/OCl-) produced by the myeloperoxidase (MPO) system and gets converted to taurine chloramine (Tau-Cl). Neutrophils have three types of granules, of which the primary granule MPO, secondary granule lactoferrin, and tertiary granule matrix metalloproteinase (MMP)-9 are released into the extracellular space by a process called degranulation. MPO produces hypochlorous acid to kill microorganisms, and the released MPO forms neutrophil extracellular traps (NETs) with released chromatin. Excessive secretion of MPO causes oxidative damage to the surrounding tissues. Lactoferrin exerts antioxidant activity, prevents pro-inflammatory pathway activation, sepsis, and tissue damages, and delays neutrophil apoptosis. Our experimental results show that neutrophils released small amount of granules in an inactive state, and phorbol 12-myristate 13-acetate (PMA) andN-formyl-methionine-leucyl-phenylalanine induced neutrophil degranulation. Tau-Cl inhibited the PMA-induced degranulation of MPO and formation of NETs. While Tau-Cl increased the degranulation of lactoferrin, it had no effect on MMP-9 degranulation. MPO negatively regulated the production of macrophage inflammatory protein (MIP)-2, which stimulates the degranulation and migration of neutrophils. Tau-Cl abrogated MIP-2 expression, suggestive of its inhibitory effect on MPO release. The increase in the intracellular level of MPO may negatively regulates MIP-2 expression, thereby contributing to the further regulation of neutrophil degranulation and migration. Here, we suggest that Tau-Cl selectively inhibits MPO degranulation and stimulates lactoferrin degranulation from neutrophils, thereby protecting inflamed tissues from oxidative damage induced by excessively released MPO.