ArticleProceedings of the National Academy of Sciences of the United States of America2013
The receptor for complement component C3a mediates protection from intestinal ischemia-reperfusion injuries by inhibiting neutrophil mobilization.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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84 citing papers in PubMed, 163 citations in OpenAlex.
- IL-6 Receptor Inhibition by Tocilizumab Attenuated Expression of C5a Receptor 1 and 2 in Non-ST-Elevation Myocardial Infarction.Frontiers in immunology · 2018Trial
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- The complement system in human pregnancy and preeclampsia.Frontiers in immunology · 2025Review
- Complement-mediated and direct activation of human neutrophils induced byFrontiers in immunology · 2025Article
- Identification of Potential Biomarkers and Immune Cell Signatures in COVID-19 Myocarditis Through Bioinformatic Analysis.Cardiology research and practice · 2025Article
- Identification and validation of mitochondrial-related genes in intestinal ischemia-reperfusion injury based on WGCNA and machine learning.Frontiers in molecular biosciences · 2025Article
- Zinc pretreatment for protection against intestinal ischemia-reperfusion injury.World journal of gastrointestinal surgery · 2024Article
- Cellular signatures in human blood track bone mineral density in postmenopausal women.JCI insight · 2024Article
- Complement C3aR signaling: Immune and metabolic modulation and its impact on Alzheimer's disease.European journal of immunology · 2024Review
- A guide to complement biology, pathology and therapeutic opportunity.Nature reviews. Immunology · 2024Review
- Molecular basis of anaphylatoxin binding, activation, and signaling bias at complement receptors.Cell · 2023Article
- Complement: Functions, location and implications.Immunology · 2023Review
- C3-dependent effector functions of complement.Immunological reviews · 2023Review
- Complement downregulation promotes an inflammatory signature that renders colorectal cancer susceptible to immunotherapy.Journal for immunotherapy of cancer · 2022Article
- The Complement System, Aging, and Aging-Related Diseases.International journal of molecular sciences · 2022Review
- C3aR plays both sides in regulating resistance to bacterial infections.PLoS pathogens · 2022Review
- Promotion of the inflammatory response in mid colon of complement component 3 knockout mice.Scientific reports · 2022Article
- In Vivo Pharmacodynamic Method to Assess Complement C5a Receptor Antagonist Efficacy.ACS pharmacology & translational science · 2022Article
- Intracellular Complement Component 3 Attenuated Ischemia-Reperfusion Injury in the Isolated Buffer-Perfused Mouse Heart and Is Associated With Improved Metabolic Homeostasis.Frontiers in immunology · 2022Article
- Mitochondrial DNA Release Contributes to Intestinal Ischemia/Reperfusion Injury.Frontiers in pharmacology · 2022Review
24 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
C3a is a key complement activation fragment, yet its neutrophil-expressed receptor (C3aR) still has no clearly defined role. In this study, we used a neutrophil-dependent mouse model of intestinal ischemia-reperfusion (IR) injury to explore the role of C3aR in acute tissue injuries. C3aR deficiency worsened intestinal injury, which corresponded with increased numbers of tissue-infiltrating neutrophils. Circulating neutrophils were significantly increased in C3aR(-/-) mice after intestinal ischemia, and C3aR(-/-) mice also mobilized more circulating neutrophils after granulocyte colony-stimulating factor infusion compared with WT mice, indicating a specific role for C3aR in constraining neutrophil mobilization in response to intestinal injury. In support of this role, C3aR(-/-) mice reconstituted with WT bone marrow reversed IR pathology back to WT levels. Complement C5a receptor (C5aR) antagonism in C3aR(-/-) mice also rectified the worsened pathology after intestinal IR injury but had no effect on circulating neutrophils, highlighting the opposing roles of C3a and C5a in disease pathogenesis. Finally, we found that using a potent C3a agonist to activate C3aR in vivo reduced neutrophil mobilization and ameliorated intestinal IR pathology in WT, but not C3aR(-/-), mice. This study identifies a role for C3aR in regulating neutrophil mobilization after acute intestinal injury and highlights C3aR agonism as a potential treatment option for acute, neutrophil-driven pathologies.
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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.