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Original Article

Korean J Physiol Pharmacol 2022; 26(4): 229-238

Published online July 1, 2022 https://doi.org/10.4196/kjpp.2022.26.4.229

Copyright © Korean J Physiol Pharmacol.

Glycine induces enhancement of bactericidal activity of neutrophils

Shin-Hae Kang1, Hwa-Yong Ham1, Chang-Won Hong2,*, and Dong-Keun Song1,*

1Department of Pharmacology, College of Medicine, Hallym University, Chuncheon 24252, 2Department of Physiology, School of Medicine, Kyungpook National University, Daegu 41944, Korea

Correspondence to:Dong-Keun Song
E-mail: dksong@hallym.ac.kr
Chang-Won Hong
E-mail: cwhong@knu.ac.kr

Author contributions: D.-K.S. and C.-W.H. conceived and designed the experiments; C.-W.H., H.-Y.H. and S.-H.K. performed the experiments and analyzed the data; D.-K.S. and C.-W.H. wrote the paper.

Received: November 24, 2021; Revised: March 30, 2022; Accepted: April 13, 2022

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Severe bacterial infections are frequently accompanied by depressed neutrophil functions. Thus, agents that increase the microbicidal activity of neutrophils could add to a direct antimicrobial therapy. Lysophosphatidylcholine augments neutrophil bactericidal activity via the glycine (Gly)/glycine receptor (GlyR) α2/TRPM2/p38 mitogen-activated protein kinase (MAPK) pathway. However, the direct effect of glycine on neutrophil bactericidal activity was not reported. In this study, the effect of glycine on neutrophil bactericidal activity was examined. Glycine augmented bactericidal activity of human neutrophils (EC50 = 238 μM) in a strychnine (a GlyR antagonist)-sensitive manner. Glycine augmented bacterial clearance in mice, which was also blocked by strychnine (0.4 mg/kg, s.c.). Glycine enhanced NADPH oxidase-mediated reactive oxygen species (ROS) production and TRPM2-mediated [Ca2+]i increase in neutrophils that had taken up E. coli . Glycine augmented Lucifer yellow uptake (fluid-phase pinocytosis) and azurophil granule-phagosome fusion in neutrophils that had taken up E. coli in an SB203580 (a p38 MAPK inhibitor)-sensitive manner. These findings indicate that glycine augments neutrophil microbicidal activity by enhancing azurophil granule-phagosome fusion via the GlyRα2/ROS/calcium/p38 MAPK pathway. We suggest that glycine could be a useful agent for increasing neutrophil bacterial clearance.

Keywords: Calcium, Glycine, Neutrophil, p38 MAPK, Reactive oxygen species