ArticleJournal of thrombosis and haemostasis : JTH2015
Carboxypeptidase B2 deficiency reveals opposite effects of complement C3a and C5a in a murine polymicrobial sepsis model.
Article in Journal of thrombosis and haemostasis : JTH, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 36 citations in OpenAlex.
- Sepsis-associated endothelial dysfunction: clinical phenotypes, biomarkers, bedside evidence, and translational implications.The Journal of clinical investigation · 2026Review
- Article
- Association of Carboxypeptidase B2 Gene Polymorphisms With Graft Loss in Kidney Transplantation.Transplantation direct · 2026Article
- Deficiencies of carboxypeptidase N and carboxypeptidase B2 have opposite effects in a virulent mouse E. coli sepsis model.Journal of thrombosis and haemostasis : JTH · 2025Article
- Sepsis-Associated Brain Dysfunction: Mechanisms, Clinical Insights, and Therapeutic Strategies.Current drug targets · 2025Review
- The dysfunction of complement and coagulation in diseases: the implications for the therapeutic interventions.MedComm · 2024Review
- Brain Expression of CPB2 and Effects of Cpb2 Deficiency in Mouse Models of Behavior.Thrombosis and haemostasis · 2024Article
- Review
- Antithrombotic Therapy: Prevention and Treatment of Atherosclerosis and Atherothrombosis.Handbook of experimental pharmacology · 2022Article
- Liver-Dependent Lung Remodeling during Systemic Inflammation Shapes Responses to Secondary Infection.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Cell type specific gene expression profiling reveals a role for complement component C3 in neutrophil responses to tissue damage.Scientific reports · 2020Article
- Article
- Deficiency of Mouse FHR-1 Homolog, FHR-E, Accelerates Sepsis, and Acute Kidney Injury Through Enhancing the LPS-Induced Alternative Complement Pathway.Frontiers in immunology · 2020Article
- Hypofibrinolysis induced by tranexamic acid does not influence inflammation and mortality in a polymicrobial sepsis model.PloS one · 2019Article
- Challenge to the Intestinal Mucosa During Sepsis.Frontiers in immunology · 2019Review
- Carboxypeptidase B2 and N play different roles in regulation of activated complements C3a and C5a in mice.Journal of thrombosis and haemostasis : JTH · 2018Article
- The immunopathology of sepsis and potential therapeutic targets.Nature reviews. Immunology · 2017Review
- Complement pathway amplifies caspase-11-dependent cell death and endotoxin-induced sepsis severity.The Journal of experimental medicine · 2016Article
- Abrogation of immune complex glomerulonephritis by native carboxypeptidase and pharmacological antagonism of the C5a receptor.Cellular & molecular immunology · 2016Article
- Complement System Part II: Role in Immunity.Frontiers in immunology · 2015Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUND AND
objectivesCarboxypeptidase B2 (CPB2) is a basic carboxypeptidase with fibrin and complement C3a and C5a as physiological substrates. We hypothesized that in polymicrobial sepsis, CPB2-deficient mice would have sustained C5a activity, leading to disease exacerbation.
methodsPolymicrobial sepsis was induced by cecal ligation and puncture (CLP).
resultsContrary to our hypothesis, Cpb2(-/-) mice had significantly improved survival, with reduced lung edema, less liver and kidney damage, and less disseminated intravascular coagulation. Hepatic pro-CPB2 was induced by CLP, leading to increased pro-CPB2 levels. Thrombomodulin present on mesothelium supported thrombin activation of pro-CPB2. Both wild-type and Cpb2(-/-) animals treated with a C5a receptor antagonist had improved survival, demonstrating that C5a was detrimental in this model. Treatment with a fibrinolysis inhibitor, tranexamic acid, caused a decrease in survival in both genotypes; however, the Cpb2(-/-) animals retained their survival advantage. Administration of a C3a receptor antagonist exacerbated the disease in both wild-type and Cpb2(-/-) mice and eliminated the survival advantage of Cpb2(-/-) mice. C5a receptor is expressed in both peritoneal macrophages and neutrophils; in contrast, C3a receptor expression is restricted to peritoneal macrophages, and C3a induced signaling in macrophages but not neutrophils.
conclusionsWhile C5a exacerbates the peritonitis, resulting in a deleterious generalized inflammatory state, C3a activation of peritoneal macrophages may limit the initial infection following CLP, thereby playing a diametrically opposing protective role in this polymicrobial sepsis model.
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