ORIGINAL RESEARCH article
Front. Immunol.
Sec. Molecular Innate Immunity
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1597423
This article is part of the Research TopicThe Role of Glycolipids and Sphingolipids in the Differentiation and Function of Innate Immune CellsView all articles
Phosphatidylglucoside regulates apoptosis of human neutrophilic lineage cells
Provisionally accepted
Noriko Yokoyama1*
Roudy Chiminch Ekyalongo1
Madoka Kage1,2
Kei Hanafusa1
Hitoshi Nakayama1
Yoshio Hirabayashi1
Kenji Takamori1
Kazuhisa Iwabuchi3*- 1Institute for Environmental and Gender-specific Medicine, Graduate School of Medicine, Juntendo University, Urayasu, Chiba, Japan
- 2Laboratory of Dermatological Physiology, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, Sakado, Saitama, Japan
- 3Faculty of Pharmacy, Juntendo University, Chiba, Japan
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Apoptosis plays a fundamental role in the regulation of immune responses mediated by neutrophils. Phosphatidylglucoside (PtdGlc), a glycosylated phospholipid abundantly expressed on the surface of human neutrophils, has been implicated in promoting both cellular differentiation and apoptosis. In the acute myeloid leukemia (AML) cell line HL-60, PtdGlc expression increases during differentiation, and treatment with the anti-PtdGlc monoclonal antibody DIM21 induces early apoptosis. To further investigate the role of PtdGlc in neutrophilic lineage cells, we examined three AML cell lines: HL-60 (AML-M2/M3), KG1 (AML-M1), and KG1a (AML-M0). PtdGlc was highly expressed in HL-60 and KG1 cells but was absent in KG1a cells. Both HL-60 and KG1 cells exhibited early apoptosis following DIM21 treatment, whereas KG1a cells remained resistant regardless of differentiation status. Notably, in KG1 cells, DIM21 induced late-stage apoptosis specifically after ATRA-mediated differentiation, and co-treatment with ATRA and DIM21 significantly enhanced this apoptotic response. Mechanistic analysis revealed that this process was independent of NADPH oxidase and Fas signaling, as neither a reactive oxygen species inhibitor nor a neutralizing anti-Fas antibody altered the apoptotic outcome. Instead, DIM21 activated caspase-3 and caspase-8, suggesting that PtdGlc mediates apoptosis through a caspase-dependent, but NADPH oxidase-and Fas-independent, pathway. Collectively, these findings provide new insight into the apoptotic signaling function of PtdGlc in neutrophilic lineage cells and highlight its potential as a novel therapeutic target in AML.
Keywords: Phosphatidylglucoside, Acute myeloid leukemia cells, Apoptosis, Cell Death, differentiation, ATRA, KG1 cells
Received: 21 Mar 2025; Accepted: 06 May 2025.
Copyright: © 2025 Yokoyama, Ekyalongo, Kage, Hanafusa, Nakayama, Hirabayashi, Takamori and Iwabuchi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Noriko Yokoyama, Institute for Environmental and Gender-specific Medicine, Graduate School of Medicine, Juntendo University, Urayasu, Chiba, Japan
Kazuhisa Iwabuchi, Faculty of Pharmacy, Juntendo University, Chiba, Japan
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