ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2013
Extracellular histones are essential effectors of C5aR- and C5L2-mediated tissue damage and inflammation in acute lung injury.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 140 papers.
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Who cites it
140 citing papers in PubMed, 210 citations in OpenAlex.
- IRF1-mediated sensing of oxidized mitochondrial DNA drives macrophage PANoptosis in lung ischemia-reperfusion injury.Apoptosis : an international journal on programmed cell death · 2026Article
- Emerging biomodels to understand the pathophysiology of sepsis and evaluate new therapeutic strategies targeting extracellular histones.Materials today. Bio · 2026Review
- The Interaction of Neutrophil Extracellular Traps and Complement in Intracerebral Hemorrhage.Cellular and molecular neurobiology · 2026Review
- Sepsis-induced immunothrombosis: from cellular crosstalk to multiple organ dysfunction.Frontiers in immunology · 2026Review
- Regulation of histones in thromboinflammation.Frontiers in immunology · 2026Review
- NETs activate the GAS6-AXL-NLRP3 axis in macrophages to drive morphine tolerance.Cell communication and signaling : CCS · 2025Article
- Article
- Screening and Identification of Neutrophil Extracellular Trap-related Diagnostic Biomarkers for Pediatric Sepsis by Machine Learning.Inflammation · 2025Article
- By activating endothelium histone H4 mediates oleic acid-induced acute respiratory distress syndrome.BMC pulmonary medicine · 2025Article
- Immunopharmacological Insights intoCurrent pharmaceutical design · 2025Review
- The impact of circulating nucleosomes on inflammation in acute lung injury.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- The complement system: A key player in the host response to infections.European journal of immunology · 2024Review
- The Impact of Extracellular Histones and Absence of Toll-like Receptors on Cardiac Functional and Electrical Disturbances in Mouse Hearts.International journal of molecular sciences · 2024Article
- Extracellular histones promote TWIK2-dependent potassium efflux and associated NLRP3 activation in alveolar macrophages during sepsis-induced lung injury.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- Macrophage-1 antigen exacerbates histone-induced acute lung injury and promotes neutrophil extracellular trap formation.FEBS open bio · 2024Article
- M6229 Protects against Extracellular-Histone-Induced Liver Injury, Kidney Dysfunction, and Mortality in a Rat Model of Acute Hyperinflammation.International journal of molecular sciences · 2024Article
- The complement cascade in lung injury and disease.Respiratory research · 2024Review
- Emerging role of C5aR2: novel insights into the regulation of uterine immune cells during pregnancy.Frontiers in immunology · 2024Article
- NETosis Is Induced by Complement Component 5a: Implications in the Pathogenesis of Pyoderma Gangrenosum.The Journal of investigative dermatology · 2024Article
- Disruption of the C5a/C5aR1 axis confers protection against hookworm infection in lung.Frontiers in immunology · 2024Article
80 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
We investigated how complement activation promotes tissue injury and organ dysfunction during acute inflammation. Three models of acute lung injury (ALI) induced by LPS, IgG immune complexes, or C5a were used in C57BL/6 mice, all models requiring availability of both C5a receptors (C5aR and C5L2) for full development of ALI. Ligation of C5aR and C5L2 with C5a triggered the appearance of histones (H3 and H4) in bronchoalveolar lavage fluid (BALF). BALF from humans with ALI contained H4 histone. Histones were absent in control BALF from healthy volunteers. In mice with ALI, in vivo neutralization of H4 with IgG antibody reduced the intensity of ALI. Neutrophil depletion in mice with ALI markedly reduced H4 presence in BALF and was highly protective. The direct lung damaging effects of extracellular histones were demonstrated by airway administration of histones into mice and rats (Sprague-Dawley), which resulted in ALI that was C5a receptor-independent, and associated with intense inflammation, PMN accumulation, damage/destruction of alveolar epithelial cells, together with release into lung of cytokines/chemokines. High-resolution magnetic resonance imaging demonstrated lung damage, edema and consolidation in histone-injured lungs. These studies confirm the destructive C5a-dependent effects in lung linked to appearance of extracellular histones.
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