ArticleJournal of immunology (Baltimore, Md. : 1950)2009
Milk fat globule epidermal growth factor-factor VIII is down-regulated in sepsis via the lipopolysaccharide-CD14 pathway.
Article in Journal of immunology (Baltimore, Md. : 1950), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 78 citations in OpenAlex.
- Top Five Stories of the Cellular Landscape and Therapies of Atherosclerosis: Current Knowledge and Future Perspectives.Current medical science · 2024Review
- Mononuclear phagocyte system-related multi-omics features yield head and neck squamous cell carcinoma subtypes with distinct overall survival, drug, and immunotherapy responses.Journal of cancer research and clinical oncology · 2024Article
- A novel opsonic eCIRP inhibitor for lethal sepsis.Journal of leukocyte biology · 2024Article
- Cellular mechanisms underlying the impairment of macrophage efferocytosis.Immunology letters · 2023Review
- MFG-E8 has guiding significance for the prognosis and treatment of sepsis.Scientific reports · 2022Article
- Drugging the efferocytosis process: concepts and opportunities.Nature reviews. Drug discovery · 2022Review
- MFG-E8 Knockout Aggravated Nonalcoholic Steatohepatitis by Promoting the Activation of TLR4/NF-Mediators of inflammation · 2022Article
- Comprehensive Analysis of circRNAs, miRNAs, and mRNAs Expression Profiles and ceRNA Networks in Decidua of Unexplained Recurrent Spontaneous Abortion.Frontiers in genetics · 2022Article
- Milk fat globule EGF factor 8 restores mitochondrial function via integrin-medicated activation of the FAK-STAT3 signaling pathway in acute pancreatitis.Clinical and translational medicine · 2021Article
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- Alterations in expression of endometrial milk fat globule-EGF factor 8 (MFG-E8) and leukemia inhibitory factor (LIF) in patients with infertility and endometriosis.JBRA assisted reproduction · 2017Article
- Article
- Milk fat globule-epidermal growth factor-factor VIII attenuates sepsis-induced acute kidney injury.The Journal of surgical research · 2017Article
- Milk fat globule epidermal growth factor 8 inhibits periodontitis in non-human primates and its gingival crevicular fluid levels can differentiate periodontal health from disease in humans.Journal of clinical periodontology · 2017Article
- The Role of Efferocytosis in Atherosclerosis.Circulation · 2017Article
- Mechanisms and Consequences of Defective Efferocytosis in Atherosclerosis.Frontiers in cardiovascular medicine · 2017Review
- Spherical nucleic acid targeting microRNA-99b enhances intestinal MFG-E8 gene expression and restores enterocyte migration in lipopolysaccharide-induced septic mice.Scientific reports · 2016Article
- Article
- Role of milk fat globule-epidermal growth factor 8 in osteoimmunology.BoneKEy reports · 2016Review
- Functional Role of Milk Fat Globule-Epidermal Growth Factor VIII in Macrophage-Mediated Inflammatory Responses and Inflammatory/Autoimmune Diseases.Mediators of inflammation · 2016Review
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
Abstract
Phagocytosis prevents the release of potentially harmful or immunogenic materials from dying cells. Milk fat globule epidermal growth factor (EGF)-factor VIII (MFG-E8) mediates the clearance of apoptotic cells. We have previously shown that the administration of MFG-E8-rich exosomes from immature dendritic cells promotes the phagocytosis of apoptotic cells and improves survival in sepsis. Because endotoxin is elevated in polymicrobial sepsis, we hypothesized that down-regulation of MFG-E8 is mediated via the LPS-CD14 pathway, eventually leading to the accruement of apoptotic cells. Polymicrobial sepsis was induced by cecal ligation and puncture (CLP) in CD14-deficient (CD14(-/-)), TLR4-mutated and wild-type (WT) mice. In addition, endotoxemia was elicited by i.p. injection of LPS. LPS was also neutralized by pretreating CLP-induced WT mice with polymyxin B. Splenic MFG-E8 expression, phagocytic activity, and apoptosis were assessed 5 and 20 h after CLP or 5 h after LPS administration. In septic WT mice, MFG-E8 mRNA and protein levels were suppressed by 49 and 33%, respectively. Endotoxemia reduced MFG-E8 mRNA expression in a dose dependent manner and the down-regulation of MFG-E8 mRNA expression in CLP-induced sepsis was attenuated by polymyxin B. This CLP-induced suppression was not observed in both CD14(-/-) and TLR4-mutated mice. CLP significantly decreased phagocytic activity of peritoneal macrophages in WT (by 30%), but not in CD14(-/-) mice. CLP also induced significant apoptosis in the spleen of WT (by 61%), but less in CD14(-/-) mice. Thus, MFG-E8 production is down-regulated in sepsis by LPS-CD14 dependent fashion, leading to a reduction of phagocytosis of apoptotic cells.
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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.