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Taurine chloramine selectively regulates neutrophil degranulation through the inhibition of myeloperoxidase and upregulation of lactoferrin

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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.

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Data availability

The datasets generated during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This work was supported by the Inha University Research Grant. We thank Dr. Young June Kim (Indiana University, Indianapolis) for helpful discussion and reviewing manuscript.

Funding

This work was supported by the Inha University Research Grant.

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Author notes

  1. Dong Gye Kim and Young Min Kwon have contributed equally to this work.

Authors and Affiliations

  1. Laboratory of Leukocyte Signaling Research, Department of Pharmacology, Inha University School of Medicine, 100 Inha-ro, Michuhol-gu, Incheon, 22212, Korea

    Dong Gye Kim, Young Min Kwon, In Soon Kang & Chaekyun Kim

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  1. Dong Gye Kim
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Contributions

CK conceived and designed the experiments, interpreted the experimental results, and prepared the manuscript; DGK and YMK performed the experiments; and DGK, YMK, and ISK analyzed the data. All authors take responsibility for the integrity of the data analysis.

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Correspondence to Chaekyun Kim.

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The authors declare that they have no conflict of interest.

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The Animal Care and Use Committee of Inha University approved this study (INHA 161214-465).

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Handling editor: S. W. Schaffer.

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Kim, D.G., Kwon, Y.M., Kang, I.S. et al. Taurine chloramine selectively regulates neutrophil degranulation through the inhibition of myeloperoxidase and upregulation of lactoferrin. Amino Acids 52, 1191–1199 (2020). https://doi.org/10.1007/s00726-020-02886-5

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