ArticleNature communications2017
Exploiting a novel conformational switch to control innate immunity mediated by complement protein C3a.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Therapeutic Targeting of the Complement System: From Rare Diseases to Pandemics.Pharmacological reviews · 2021Pooled it
- Immune-activating PTL/nanowire composite coating on Ti surface enables macrophage-driven bacterial clearance and osseointegration.Bioactive materials · 2026Article
- The Influence of Anti-C3aR and Anti-C5aR Antibody Levels on the Course of Specific Glomerulonephritis Types.Journal of clinical medicine · 2025Article
- Knockdown of C3aR alleviates age-related bone loss via activation of YAP1/β-catenin signaling.The Journal of biological chemistry · 2025Article
- The complement system in human pregnancy and preeclampsia.Frontiers in immunology · 2025Review
- The Relationship between Complements and Age-Related Macular Degeneration and Its Pathogenesis.Journal of ophthalmology · 2024Review
- Africanized honeybee venom (Frontiers in immunology · 2024Article
- Role of Complement in the Onset of Age-Related Macular Degeneration.Biomolecules · 2023Review
- Drug delivery targets and strategies to address mast cell diseases.Expert opinion on drug delivery · 2023Review
- The Complement System, Aging, and Aging-Related Diseases.International journal of molecular sciences · 2022Review
- Novel Fluorescence-Based High-Throughput FLIPR Assay Utilizing Membrane-Tethered Genetic Calcium Sensors to Identify T-Type Calcium Channel Modulators.ACS pharmacology & translational science · 2022Article
- The biological alterations of synapse/synapse formation in sepsis-associated encephalopathy.Frontiers in synaptic neuroscience · 2022Review
- The complement system in age-related macular degeneration.Cellular and molecular life sciences : CMLS · 2021Review
- C5a-C5aR1 Axis Activation Drives Envenomation Immunopathology by the SnakeFrontiers in immunology · 2021Article
- Complement Component C3: A Novel Biomarker Participating in the Pathogenesis of Non-alcoholic Fatty Liver Disease.Frontiers in medicine · 2021Review
- Mitochondrial C3a Receptor Activation in Oxidatively Stressed Epithelial Cells Reduces Mitochondrial Respiration and Metabolism.Frontiers in immunology · 2021Article
- Endothelial progenitor cell transplantation alleviated ischemic brain injury via inhibiting C3/C3aR pathway in mice.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2020Article
- Article
- The Role of Complement C3a Receptor in Stroke.Neuromolecular medicine · 2019Review
- Cromolyn sodium delays disease onset and is neuroprotective in the SOD1Scientific reports · 2019Article
Corrections and comments
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Complement C3a is an important protein in innate and adaptive immunity, but its specific roles in vivo remain uncertain because C3a degrades rapidly to form the C3a-desArg protein, which does not bind to the C3a receptor and is indistinguishable from C3a using antibodies. Here we develop the most potent, stable and highly selective small molecule modulators of C3a receptor, using a heterocyclic hinge to switch between agonist and antagonist ligand conformations. This enables characterization of C3 areceptor-selective pro- vs. anti-inflammatory actions in human mast cells and macrophages, and in rats. A C3a receptor-selective agonist induces acute rat paw inflammation by first degranulating mast cells before activating macrophages and neutrophils. An orally administered C3a receptor-selective antagonist inhibits mast cell degranulation, thereby blocking recruitment and activation of macrophages and neutrophils, expression of inflammatory mediators and inflammation in a rat paw edema model. These novel tools reveal the mechanism of C3a-induced inflammation and provide new insights to complement-based medicines.Complement C3a is an important protein in innate and adaptive immunity, but its roles in vivo are unclear. Here the authors develop novel chemical agonists and antagonists for the C3a receptor, and show that they modulate mast cell degranulation and inflammation in a rat paw edema model.
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