ArticleMolecular immunology2008
Disruption of the C5a receptor gene increases resistance to acute Gram-negative bacteremia and endotoxic shock: opposing roles of C3a and C5a.
Article in Molecular immunology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 72 citations in OpenAlex.
- C5aR1 Inhibition Alleviates Cranial Radiation-Induced Cognitive Decline.Cancer research · 2026Article
- Immunomodulatory and cardio-protective effects of differentially originated multipotent mesenchymal stroma cells during polymicrobial sepsis in mice.European journal of trauma and emergency surgery : official publication of the European Trauma Society · 2025Article
- Complement anaphylatoxins: Potential therapeutic target for diabetic kidney disease.Diabetic medicine : a journal of the British Diabetic Association · 2025Review
- Multi-Target Peptide Nanofiber Immunotherapy Diminishes Complement Anaphylatoxin Activity in Acute Inflammation.Advanced healthcare materials · 2025Article
- Identification of a genetic region linked to tolerance to MRSA infection using Collaborative Cross mice.PLoS genetics · 2024Article
- Salmonella manipulates the host to drive pathogenicity via induction of interleukin 1β.PLoS biology · 2024Article
- Influence of complement protein C1q or complement receptor C5aR1 on gut microbiota composition in wildtype and Alzheimer's mouse models.Journal of neuroinflammation · 2023Article
- Modulation of C5a-C5aR1 signaling alters the dynamics of AD progression.Journal of neuroinflammation · 2022Article
- 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
- Harnessing the Power of Mast Cells in unconventional Immunotherapy Strategies and Vaccine Adjuvants.Cells · 2020Review
- The Complement C3a and C3a Receptor Pathway in Kidney Diseases.Frontiers in immunology · 2020Review
- The Second Receptor for C5a, C5aR2, Is Detrimental to Mice during Systemic Infection withJournal of immunology (Baltimore, Md. : 1950) · 2019Article
- Complement receptor C3aR1 controls neutrophil mobilization following spinal cord injury through physiological antagonism of CXCR2.JCI insight · 2019Article
- New tricks for an ancient system: Physiological and pathological roles of complement in the CNS.Molecular immunology · 2018Review
- Shuang-Huang-Lian injection induces an immediate hypersensitivity reaction via C5a but not IgE.Scientific reports · 2018Article
- Complement regulation and kidney diseases: recent knowledge of the double-edged roles of complement activation in nephrology.Clinical and experimental nephrology · 2018Review
- The distinct function of Tep2 and Tep6 in the immune defense of Drosophila melanogaster against the pathogen Photorhabdus.Virulence · 2017Article
- C5a/C5aR Pathway Plays a Vital Role in Brain Inflammatory Injury via Initiating Fgl-2 in Intracerebral Hemorrhage.Molecular neurobiology · 2017Article
- Prevention of C5aR1 signaling delays microglial inflammatory polarization, favors clearance pathways and suppresses cognitive loss.Molecular neurodegeneration · 2017Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The host response to intravascular, Gram-negative bacteria includes profound immunologic, hematologic and physiologic changes. Numerous host defense mechanisms are activated by Gram-negative bacteria, including the complement system. Activation of the complement system leads to cleavage of C5 with subsequent generation of the C5a anaphylatoxin peptide. C5a mediates potent, proinflammatory activities by binding to the C5a receptor (C5aR, CD88). In this study, we report the targeted disruption of the murine C5aR gene (C5aR-/- mice) and define the role of the C5aR in a model of Gram-negative bacteremia. Following an intravenous infusion of heat-killed Escherichia coli, the C5aR-/- mice were completely protected from the mortality suffered by their wild-type littermates (P<0.001). The C5aR-/- mice were also significantly (P=0.008) more resistant to mortality following an intravenous infusion of purified E. coli endotoxin compared to the wild-type littermates. In addition, the C5aR-/- mice were resistant to the thrombocytopenia and hemoconcentration observed in wild-type animals. Lethality in the wild-type mice was reversed by pre-treatment with either the histamine antagonist diphenhydramine or triprolidine. The wild-type littermates were also rescued following pre-treatment with the basophil and mast cell-stabilizing agent - cromolyn sodium. Collectively, these data demonstrate that not only is the absence of the C5aR protective in E. coli bacteremia, but that C5aR-dependent histamine release plays a major role in shock induced by Gram-negative septicemia. Moreover, they provide additional in vivo evidence that C3a and C5a have divergent biological functions in Gram-negative bacteremia and shock.
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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.