ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2010
C5a alters blood-brain barrier integrity in experimental lupus.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 1 of them a synthesis that pooled it.
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Who cites it
64 citing papers in PubMed, 1 synthesis or guideline pooled it, 113 citations in OpenAlex.
- Peripheral complement proteins in schizophrenia: A systematic review and meta-analysis of serological studies.Schizophrenia research · 2020Pooled it
- Intestinal and Blood-Brain Barrier Dysfunction in Lupus: Emerging Mechanisms and Modulation by Cinnamon.Molecules (Basel, Switzerland) · 2026Review
- Immunopathogenesis of neuropsychiatric systemic lupus erythematosus: current insights into inflammatory and thrombotic pathways.Journal of neuroinflammation · 2026Review
- Shifting From Systemic to Precision-Targeted Complement Therapies: Opportunities and Hurdles.European journal of immunology · 2026Review
- Complement in brain and eye disease: shared mechanisms, convergent pathologies, and common therapeutic opportunities.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- Neuro-Immune Crosstalk: Molecular Mechanisms, Biological Functions, Diseases, and Therapeutic Targets.MedComm · 2026Review
- Stem cell-derived extracellular vesicles as immunomodulatory agents: targeting pathological crosstalk in systemic lupus erythematosus and multiple sclerosis.Frontiers in medicine · 2026Review
- Emerging role of complement system in the induction of neuroinflammation in adenylosuccinate lyase deficiency disorder.Brain, behavior, & immunity - health · 2025Review
- Antiviral resistance and barrier integrity at the maternal-fetal interface restrict hepatitis E virus from crossing the placental barrier.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Review
- The role of microglia and complement C5/C5a in the pathogenesis of rhegmatogenous retinal detachment with choroidal detachment.Computational and structural biotechnology journal · 2025Article
- Complement activation in immunological neurological disorders: mechanisms and therapeutic strategies.Frontiers in neurology · 2025Review
- Animal models of neuropsychiatric systemic lupus erythematosus: deciphering the complexity and guiding therapeutic development.Autoimmunity · 2024Review
- Diagnosis and Management of Pediatric Neuropsychiatric Systemic Lupus Erythematosus: An Update.Paediatric drugs · 2024Review
- Complement: Functions, location and implications.Immunology · 2023Review
- Centrally acting ACE inhibitor (cACEi) and angiotensin receptor blocker (cARB) use and cognitive dysfunction in patients with SLE.Lupus science & medicine · 2023Article
- Exploring Pro-Inflammatory Immunological Mediators: Unraveling the Mechanisms of Neuroinflammation in Lysosomal Storage Diseases.Biomedicines · 2023Review
- Complement: The Road Less Traveled.Journal of immunology (Baltimore, Md. : 1950) · 2023Review
- Mouse models, antibodies, and neuroimaging: Current knowledge and future perspectives in neuropsychiatric systemic lupus erythematosus (NPSLE).Frontiers in psychiatry · 2023Review
- Targeting the Complement-Sphingolipid System in COVID-19 and Gaucher Diseases: Evidence for a New Treatment Strategy.International journal of molecular sciences · 2022Review
4 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The blood-brain barrier (BBB) is a crucial anatomic location in the brain. Its dysfunction complicates many neurodegenerative diseases, from acute conditions, such as sepsis, to chronic diseases, such as systemic lupus erythematosus (SLE). Several studies suggest an altered BBB in lupus, but the underlying mechanism remains unknown. In the current study, we observed a definite loss of BBB integrity in MRL/MpJ-Tnfrsf6(lpr) (MRL/lpr) lupus mice by IgG infiltration into brain parenchyma. In line with this result, we examined the role of complement activation, a key event in this setting, in maintenance of BBB integrity. Complement activation generates C5a, a molecule with multiple functions. Because the expression of the C5a receptor (C5aR) is significantly increased in brain endothelial cells treated with lupus serum, the study focused on the role of C5a signaling through its G-protein-coupled receptor C5aR in brain endothelial cells, in a lupus setting. Reactive oxygen species production increased significantly in endothelial cells, in both primary cells and the bEnd3 cell line treated with lupus serum from MRL/lpr mice, compared with those treated with control serum from MRL(+/+) mice. In addition, increased permeability monitored by changes in transendothelial electrical resistance, cytoskeletal remodeling caused by actin fiber rearrangement, and increased iNOS mRNA expression were observed in bEnd3 cells. These disruptive effects were alleviated by pretreating cells with a C5a receptor antagonist (C5aRant) or a C5a antibody. Furthermore, the structural integrity of the vasculature in MRL/lpr brain was maintained by C5aR inhibition. These results demonstrate the regulation of BBB integrity by the complement system in a neuroinflammatory setting. For the first time, a novel role of C5a in the maintenance of BBB integrity is identified and the potential of C5a/C5aR blockade highlighted as a promising therapeutic strategy in SLE and other neurodegenerative diseases.
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Registered trials
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.