Phosphatidylglucoside regulates apoptosis of human neutrophilic lineage cells
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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1597423/full |
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| author | Noriko Yokoyama Roudy Chiminch Ekyalongo Madoka Kage Madoka Kage Kei Hanafusa Kei Hanafusa Hitoshi Nakayama Hitoshi Nakayama Hitoshi Nakayama Yoshio Hirabayashi Yoshio Hirabayashi Kenji Takamori Kazuhisa Iwabuchi Kazuhisa Iwabuchi |
| author_facet | Noriko Yokoyama Roudy Chiminch Ekyalongo Madoka Kage Madoka Kage Kei Hanafusa Kei Hanafusa Hitoshi Nakayama Hitoshi Nakayama Hitoshi Nakayama Yoshio Hirabayashi Yoshio Hirabayashi Kenji Takamori Kazuhisa Iwabuchi Kazuhisa Iwabuchi |
| author_sort | Noriko Yokoyama |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-35f3bc713bf54f3cb94b7c368850d6cc |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-35f3bc713bf54f3cb94b7c368850d6cc2025-08-20T03:48:27ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-05-011610.3389/fimmu.2025.15974231597423Phosphatidylglucoside regulates apoptosis of human neutrophilic lineage cellsNoriko Yokoyama0Roudy Chiminch Ekyalongo1Madoka Kage2Madoka Kage3Kei Hanafusa4Kei Hanafusa5Hitoshi Nakayama6Hitoshi Nakayama7Hitoshi Nakayama8Yoshio Hirabayashi9Yoshio Hirabayashi10Kenji Takamori11Kazuhisa Iwabuchi12Kazuhisa Iwabuchi13Institute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, Chiba, JapanInstitute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, Chiba, JapanInstitute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, Chiba, JapanLaboratory of Dermatological Physiology, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, Saitama, JapanInstitute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, Chiba, JapanLaboratory of Biochemistry, Faculty of Pharmacy, Juntendo University, Urayasu, Chiba, JapanInstitute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, Chiba, JapanInfection Control Nursing, Juntendo University Graduate School of Health Care and Nursing, Chiba, JapanLaboratory of Biochemistry, Juntendo University Faculty of Health Care and Nursing, Chiba, JapanInstitute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, Chiba, JapanCellular Informatics Lab, RIKEN, Saitama, JapanInstitute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, Chiba, JapanInstitute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, Chiba, JapanLaboratory of Biochemistry, Faculty of Pharmacy, Juntendo University, Urayasu, Chiba, JapanApoptosis 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.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1597423/fullphosphatidylglucosideacute myeloid leukemia cellsapoptosiscell deathdifferentiationATRA |
| spellingShingle | Noriko Yokoyama Roudy Chiminch Ekyalongo Madoka Kage Madoka Kage Kei Hanafusa Kei Hanafusa Hitoshi Nakayama Hitoshi Nakayama Hitoshi Nakayama Yoshio Hirabayashi Yoshio Hirabayashi Kenji Takamori Kazuhisa Iwabuchi Kazuhisa Iwabuchi Phosphatidylglucoside regulates apoptosis of human neutrophilic lineage cells Frontiers in Immunology phosphatidylglucoside acute myeloid leukemia cells apoptosis cell death differentiation ATRA |
| title | Phosphatidylglucoside regulates apoptosis of human neutrophilic lineage cells |
| title_full | Phosphatidylglucoside regulates apoptosis of human neutrophilic lineage cells |
| title_fullStr | Phosphatidylglucoside regulates apoptosis of human neutrophilic lineage cells |
| title_full_unstemmed | Phosphatidylglucoside regulates apoptosis of human neutrophilic lineage cells |
| title_short | Phosphatidylglucoside regulates apoptosis of human neutrophilic lineage cells |
| title_sort | phosphatidylglucoside regulates apoptosis of human neutrophilic lineage cells |
| topic | phosphatidylglucoside acute myeloid leukemia cells apoptosis cell death differentiation ATRA |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1597423/full |
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