Taurine chloramine selectively regulates neutrophil degranulation through the inhibition of myeloperoxidase and upregula
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ORIGINAL ARTICLE
Taurine chloramine selectively regulates neutrophil degranulation through the inhibition of myeloperoxidase and upregulation of lactoferrin Dong Gye Kim1 · Young Min Kwon1 · In Soon Kang1 · Chaekyun Kim1 Received: 28 May 2020 / Accepted: 21 August 2020 © Springer-Verlag GmbH Austria, part of Springer Nature 2020
Abstract 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) and N-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. Keywords Neutrophil · Taurine chloramine · Myeloperoxidase · Lactoferrin · Neutrophil extracellular traps · Macrophage inflammatory protein-2
Introduction
Handling editor: S. W. Schaffer. Dong Gye Kim and Young Min Kwon have contributed equally to this work. * Chaekyun Kim [email protected] 1
Laboratory of Leukocyte Signaling Research, Department of Pharmacology, Inha University School of Medicine, 100 Inha‑ro, Michuhol‑gu, Incheon 22212, Korea
Taurine is one of the most abundant free amino acids in neutrophils (Schuller-Levis and Park 2003) that is known to react with hypochlorous acid (HOCl/OCl−) produced by the myeloperoxidase (MPO) system to form taurine chloramine (Tau-Cl) (Kim and Cha 2014). MPO produces HOCl in a reaction between hydrogen peroxid
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