ArticleMolecular medicine (Cambridge, Mass.)2012
Extracellular histones inhibit efferocytosis.
Article in Molecular medicine (Cambridge, Mass.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 49 citations in OpenAlex.
- DAMP signaling networks: from receptors to diverse pathophysiological functions.Journal of advanced research · 2026Review
- From inside to outside: exploring extracellular antimicrobial histone-derived peptides as multi-talented molecules.The Journal of antibiotics · 2024Review
- Extracellular mixed histones are neurotoxic and modulate select neuroimmune responses of glial cells.PloS one · 2024Article
- Cellular mechanisms underlying the impairment of macrophage efferocytosis.Immunology letters · 2023Review
- Sputum from patients with primary ciliary dyskinesia contains high numbers of dysfunctional neutrophils and inhibits efferocytosis.Respiratory research · 2022Article
- Inhaled Pro-Efferocytic Nanozymes Promote Resolution of Acute Lung Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Nrf2 Is Required for Optimal Alveolar-Macrophage-Mediated Apoptotic Neutrophil Clearance after Oxidant Injury.Antioxidants (Basel, Switzerland) · 2022Article
- Article
- Inhibition of Efferocytosis by Extracellular CIRP-Induced Neutrophil Extracellular Traps.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- The Phagocytic Code Regulating Phagocytosis of Mammalian Cells.Frontiers in immunology · 2021Review
- Bovine Neutrophils Release Extracellular Traps and Cooperate With Macrophages inFrontiers in immunology · 2021Article
- Regulation of Apoptotic Cell Clearance During Resolution of Inflammation.Frontiers in pharmacology · 2019Review
- Article
- Biology, role and therapeutic potential of circulating histones in acute inflammatory disorders.Journal of cellular and molecular medicine · 2018Review
- Article
- PAD4 Deficiency Decreases Inflammation and Susceptibility to Pregnancy Loss in a Mouse Model.Biology of reproduction · 2016Article
- Clearance of apoptotic neutrophils and resolution of inflammation.Immunological reviews · 2016Review
- [Damage-associated molecular patterns and liver failure].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2016Review
- Caco-2 cells infected with rotavirus release extracellular vesicles that express markers of apoptotic bodies and exosomes.Cell stress & chaperones · 2015Article
- Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
The uptake and clearance of apoptotic cells by macrophages and other phagocytic cells, a process called efferocytosis, is a major component in the resolution of inflammation. Increased concentrations of extracellular histones are found during acute inflammatory states and appear to contribute to organ system dysfunction and mortality. In these studies, we examined the potential role of histones in modulating efferocytosis. We found that phagocytosis of apoptotic neutrophils or thymocytes by macrophages was significantly diminished in the presence of histones H3 or H4, but not histone H1. Histone H3 demonstrated direct binding to macrophages, an effect that was diminished by preincubation of macrophages with the opsonins growth arrest-specific gene 6 (Gas6) and milk fat globule-epidermal growth factor (EGF) 8 (MFG-E8). Incubation of histone H3 with soluble α(v)β₅ integrin and Mer, but not with α(v)β₃, diminished its binding to macrophages. Phagocytosis of apoptotic cells by alveolar macrophages in vivo was diminished in the presence of histone H3. Incubation of histone H3 with activated protein C, a treatment that degrades histones, abrogated its inhibitory effects on efferocytosis under both in vitro and in vivo conditions. The present studies demonstrate that histones have inhibitory effects on efferocytosis, suggesting a new mechanism by which extracellular histones contribute to acute inflammatory processes and tissue injury.
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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.