Lysophosphatidylcholine increases neutrophil bactericidal activity by enhancement of azurophil granule-phagosome fusion via glycine.GlyR alpha 2/TRPM2/p38 MAPK signaling - PubMed (original) (raw)

. 2010 Apr 15;184(8):4401-13.

doi: 10.4049/jimmunol.0902814. Epub 2010 Mar 17.

Taek-Keun Kim, Hwa-Yong Ham, Ju-Suk Nam, Yong Ho Kim, Haifeng Zheng, Bo Pang, Tae-Kwon Min, Jun-Sub Jung, Si-Nae Lee, Hyun-Jeong Cho, Ee-Jin Kim, In-Hwan Hong, Tae-Cheon Kang, Jongho Lee, Seog Bae Oh, Sung Jun Jung, Sung Joon Kim, Dong-Keun Song

Affiliations

• PMID: 20237295
• DOI: 10.4049/jimmunol.0902814

Lysophosphatidylcholine increases neutrophil bactericidal activity by enhancement of azurophil granule-phagosome fusion via glycine.GlyR alpha 2/TRPM2/p38 MAPK signaling

Chang-Won Hong et al. J Immunol. 2010.

Abstract

Neutrophils are the first-line defense against microbes. Enhancing the microbicidal activity of neutrophils could complement direct antimicrobial therapy for controlling intractable microbial infections. Previously, we reported that lysophosphatidylcholine (LPC), an endogenous lipid, enhances neutrophil bactericidal activity (Yan et al. 2004. Nat. Med. 10: 161-167). In this study we show that LPC enhancement of neutrophil bactericidal activity is dependent on glycine, and is mediated by translocation of intracellularly located glycine receptor (GlyR) alpha2 to the plasma membrane, and subsequent increase in azurophil granule-phagosome fusion/elastase release. LPC induced GlyRalpha2-mediated [Cl(-)](i) increase, leading to transient receptor potential melastatin (TRPM)2-mediated Ca(2+) influx. Studies using human embryonic kidney 293 cells heterologously expressing TRPM2 and neutrophils showed that TRPM2 channel activity is sensitive to [Cl(-)](i). Finally, LPC induced p38 MAPK phosphorylation in an extracellular calcium/glycine dependent manner. SB203580, a p38 MAPK inhibitor, blocked LPC-induced enhancement in Lucifer yellow uptake, azurophil granule-phagosome fusion, and bactericidal activity. These results propose that enhancement of azurophil granule-phagosome fusion via GlyRalpha2/TRPM2/p38 MAPK signaling is a novel target for enhancement of neutrophil bactericidal activity.

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