The Korean Journal of Physiology and Pharmacology

  • 제26권4호
  • /
  • Pages.229-238
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  • 2022
  • /
  • 1226-4512(pISSN)
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  • 2093-3827(eISSN)
대한약리학회 (The Korean Society of Pharmacology)
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Glycine induces enhancement of bactericidal activity of neutrophils

  • Kang, Shin-Hae (Department of Pharmacology, College of Medicine, Hallym University) ;
  • Ham, Hwa-Yong (Department of Pharmacology, College of Medicine, Hallym University) ;
  • Hong, Chang-Won (Department of Physiology, School of Medicine, Kyungpook National University) ;
  • Song, Dong-Keun (Department of Pharmacology, College of Medicine, Hallym University)
  • 투고 : 2021.11.24
  • 심사 : 2022.04.13
  • 발행 : 2022.07.01
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초록

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.

키워드

과제정보

This research was supported by the Basic Research Program of the National Research Foundation of Korea (NRF), funded by the Ministry of Science ICT (NRF-2020R1F1A1067708).

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