ArticleCell death and differentiation2014
Oxidatively modified phosphatidylserines on the surface of apoptotic cells are essential phagocytic 'eat-me' signals: cleavage and inhibition of phagocytosis by Lp-PLA2.
Article in Cell death and differentiation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
64 citing papers in PubMed, 1 synthesis or guideline pooled it, 88 citations in OpenAlex.
- Ferroptosis and tumor immunity.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2024Pooled it
- Silencing arachidonate 15-lipoxygenase alleviates hypoxia-induced cognitive impairment through the mediation of phospholipase A2 group IVC-LPC18:0 to suppress ferroptosis.Molecular biomedicine · 2026Article
- The role of ferroptosis in the pathogenesis and treatment of breast cancer.Journal of translational medicine · 2026Review
- FerroScore: a statistical approach for quantifying tumor-related ferroptosis based on omics data.Briefings in bioinformatics · 2026Article
- Ferroptosis: The Demise of Cells Through Phospholipid Peroxidation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Ferroptosis at the intersection of radiotherapy and immunotherapy.Cancer metastasis reviews · 2025Review
- Ferroptosis meets cancer immunotherapy: Overcoming the crosstalk challenges through advanced drug delivery strategies.Acta pharmaceutica Sinica. B · 2025Review
- Aβ Deposition in Extracellular Space Disrupts Glial-Neuron Communication and Triggers Alzheimer's Disease.Aging and disease · 2025Review
- Athlete's Heart Revisited: Historical, Clinical, and Molecular Perspectives.Circulation research · 2025Review
- Lipotoxicity, lipid peroxidation and ferroptosis: a dilemma in cancer therapy.Cell biology and toxicology · 2025Review
- Crosstalk between ferroptosis and macrophages: potential value for targeted treatment in diseases.Molecular and cellular biochemistry · 2024Review
- Lipid Quality Control and Ferroptosis: From Concept to Mechanism.Annual review of biochemistry · 2024Review
- Advances in research on immunocyte iron metabolism, ferroptosis, and their regulatory roles in autoimmune and autoinflammatory diseases.Cell death & disease · 2024Review
- Application of Antioxidant Compounds in Bone Defect Repair.Antioxidants (Basel, Switzerland) · 2024Review
- Phosphatidylserine and/or Sialic Acid Modified Liposomes Increase Uptake by Tumor-associated Macrophages and Enhance the Anti-tumor Effect.AAPS PharmSciTech · 2024Article
- Nano-modified viruses prime the tumor microenvironment and promote the photodynamic virotherapy in liver cancer.Journal of biomedical science · 2024Article
- ROS signaling in innate immunity via oxidative protein modifications.Frontiers in immunology · 2024Review
- The crosstalk between ferroptosis and anti-tumor immunity in the tumor microenvironment: molecular mechanisms and therapeutic controversy.Cancer communications (London, England) · 2023Review
- The lipoprotein-associated phospholipase A2 inhibitor Darapladib sensitises cancer cells to ferroptosis by remodelling lipid metabolism.Nature communications · 2023Article
- Redox regulation of the immune response.Cellular & molecular immunology · 2022Review
4 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
Diversified anionic phospholipids, phosphatidylserines (PS), externalized to the surface of apoptotic cells are universal phagocytic signals. However, the role of major PS metabolites, such as peroxidized species of PS (PSox) and lyso-PS, in the clearance of apoptotic cells has not been rigorously evaluated. Here, we demonstrate that H2O2 was equally effective in inducing apoptosis and externalization of PS in naive HL60 cells and in cells enriched with oxidizable polyunsaturated species of PS (supplemented with linoleic acid (LA)). Despite this, the uptake of LA-supplemented cells by RAW264.7 and THP-1 macrophages was more than an order of magnitude more effective than that of naive cells. A similar stimulation of phagocytosis was observed with LA-enriched HL60 cells and Jurkat cells triggered to apoptosis with staurosporine. This was due to the presence of PSox on the surface of apoptotic LA-supplemented cells (but not of naive cells). This enhanced phagocytosis was dependent on activation of the intrinsic apoptotic pathway, as no stimulation of phagocytosis occurred in LA-enriched cells challenged with Fas antibody. Incubation of apoptotic cells with lipoprotein-associated phospholipase A2 (Lp-PLA2), a secreted enzyme with high specificity towards PSox, hydrolyzed peroxidized PS species in LA-supplemented cells resulting in the suppression of phagocytosis to the levels observed for naive cells. This suppression of phagocytosis by Lp-PLA2 was blocked by a selective inhibitor of Lp-PLA2, SB-435495. Screening of possible receptor candidates revealed the ability of several PS receptors and bridging proteins to recognize both PS and PSox, albeit with diverse selectivity. We conclude that PSox is an effective phagocytic 'eat-me' signal that participates in the engulfment of cells undergoing intrinsic apoptosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.