ArticlePloS one2012
MFG-E8 released by apoptotic endothelial cells triggers anti-inflammatory macrophage reprogramming.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed.
- Adipose tissue-derived MFG-E8 promotes hepatic inflammation and fibrosis through macrophage activation in a mouse MASH model.npj metabolic health and disease · 2026Article
- Preliminary exploration of mRNA, lncRNA, and miRNA expressions in the bovine jejunum unveils novel aspects of Mycobacterium avium subspecies paratuberculosis infections.BMC genomics · 2025Article
- Efferocytosis: The Janus-Faced Gatekeeper of Aging and Tumor Fate.Aging cell · 2025Review
- Recent advances in adipose-derived mesenchymal stem cell-derived exosomes for regulating macrophage polarization.Frontiers in immunology · 2025Review
- Immune-privileged tissues formed from immunologically cloaked mouse embryonic stem cells survive long term in allogeneic hosts.Nature biomedical engineering · 2024Article
- MFGE8 in exosomes derived from mesenchymal stem cells prevents esophageal stricture after endoscopic submucosal dissection in pigs.Journal of nanobiotechnology · 2024Article
- Small extracellular vesicles from Ptpn1-deficient macrophages alleviate intestinal inflammation by reprogramming macrophage polarization via lactadherin enrichment.Redox biology · 2022Article
- Milk fat-globule epidermal growth factor 8: A potential Regulator of Cutaneous Wound Healing.Molecular biology reports · 2022Review
- Article
- MFG-E8 Reduces Aortic Intimal Proliferation in a Murine Model of Transplant Vasculopathy.International journal of molecular sciences · 2022Article
- Protective Effect of MFG-E8 on Necroptosis-Induced Intestinal Inflammation and Enteroendocrine Cell Function in Diabetes.Nutrients · 2022Article
- Anti-inflammatory and immunomodulatory effects of the extracellular vesicles derived from human umbilical cord mesenchymal stem cells on osteoarthritis via M2 macrophages.Journal of nanobiotechnology · 2022Article
- Efferocytosis of vascular cells in cardiovascular disease.Pharmacology & therapeutics · 2022Review
- MFGE8 mitigates brain injury in a rat model of SAH by maintaining vascular endothelial integrity via TIGβ5/PI3K/CXCL12 signaling.Experimental brain research · 2021Article
- MFG-E8 Regulates Vascular Smooth Muscle Cell Migration Through Dose-Dependent Mediation of Actin Polymerization.Journal of the American Heart Association · 2021Article
- A bi-directional dialog between vascular cells and monocytes/macrophages regulates tumor progression.Cancer metastasis reviews · 2021Review
- Phagocytic clearance of apoptotic, necrotic, necroptotic and pyroptotic cells.Biochemical Society transactions · 2021Review
- Dermal fibroblast phagocytosis of apoptotic cells: A novel pathway for wound resolution.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Cancer Stem Cells: Emerging Key Players in Immune Evasion of Cancers.Frontiers in cell and developmental biology · 2021Review
- DCI after Aneurysmal Subarachnoid Hemorrhage Is Related to the Expression of MFG-E8.BioMed research international · 2021Article
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Apoptotic endothelial cells are an important component of the "response to injury" process. Several atherosclerosis risk factors such as hyperglycemia and oxidized low-density lipoproteins, and immune injuries, such as antibodies and complement, induce endothelial cell apoptosis. While endothelial cell apoptosis is known to affect neighboring vascular wall cell biology, its consequences on macrophage reprogramming are ill defined. In this study, we report that apoptosis of human and mouse endothelial cells triggers the release of milk fat globule-epidermal growth factor 8 (MFG-E8) and reprograms macrophages into an anti-inflammatory cells. We demonstrated that MFG-E8 is released by apoptotic endothelial cells in a caspase-3-dependent manner. When macrophages were exposed to conditioned media from serum-starved apoptotic endothelial cells, they adopt a high anti-inflammatory, low pro-inflammatory cytokine/chemokine secreting phenotype that is lost if MFG-E8 is absent from the media. Macrophage treatment with recombinant MFG-E8 recapitulates the effect of conditioned media. Finally, we showed that MFG-E8-mediated reprogramming of macrophages occurs through increased phosphorylation of signal transducer and activator of transcription-3 (STAT-3). Taken together, our study suggests a key role of MFG-E8 release from apoptotic endothelial cells in macrophage reprogramming and demonstrates the importance of the apoptotic microenvironment in anti-inflammatory macrophage responses.
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