ArticleProceedings of the National Academy of Sciences of the United States of America2013
Targeting complement component 5a promotes vascular integrity and limits airway remodeling.
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 47 papers.
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Who cites it
47 citing papers in PubMed.
- New insights into the role of complement system in colorectal cancer (Review).Molecular medicine reports · 2025Review
- TSG-6 expression distinguishes rejected and non-rejected human lung transplants: a retrospective study.Frontiers in immunology · 2025Article
- Bronchial anastomotic complications as a microvascular disruption in a mouse model of airway transplantation.Frontiers in immunology · 2025Review
- Quantitative assessment of redness in Asian patients with recurrent blepharitis: the utility of cross-polarized light.Frontiers in medicine · 2025Article
- Monitoring regulatory T cells as a prognostic marker in lung transplantation.Frontiers in immunology · 2023Review
- Elevated Cytokine Levels in Plasma of Patients with SARS-CoV-2 Do Not Contribute to Pulmonary Microvascular Endothelial Permeability.Microbiology spectrum · 2022Article
- Targeting Interleukin-10 Restores Graft Microvascular Supply and Airway Epithelium in Rejecting Allografts.International journal of molecular sciences · 2022Article
- The role of human C5a as a non-genomic target in corticosteroid therapy for management of severe COVID19.Computational biology and chemistry · 2021Article
- Article
- Neuroprotective versus Neuroinflammatory Roles of Complement: From Development to Disease.Trends in neurosciences · 2021Review
- Adipsin of the Alternative Complement Pathway Is a Potential Predictor for Preeclampsia in Early Pregnancy.Frontiers in immunology · 2021Article
- C5a-C5aR1 Axis Activation Drives Envenomation Immunopathology by the SnakeFrontiers in immunology · 2021Article
- Crosstalk between coagulation and complement activation promotes cardiac dysfunction in arrhythmogenic right ventricular cardiomyopathy.Theranostics · 2021Article
- Edematous myositis: a clinical presentation first suggesting dermatomyositis diagnosis.Brain pathology (Zurich, Switzerland) · 2020Observational
- Complement Deficiencies Result in Surrogate Pathways of Complement Activation in Novel Polygenic Lupus-like Models of Kidney Injury.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Recent advances into the role of pattern recognition receptors in transplantation.Cellular immunology · 2020Review
- Hypoxia-induced complement dysregulation is associated with microvascular impairments in mouse tracheal transplants.Journal of translational medicine · 2020Article
- IPSE, an abundant egg-secreted protein of the carcinogenic helminthInfectious agents and cancer · 2020Article
- iPSC-derived MSC therapy induces immune tolerance and supports long-term graft survival in mouse orthotopic tracheal transplants.Stem cell research & therapy · 2019Article
- High Concentration of C5a-Induced Mitochondria-Dependent Apoptosis in Murine Kidney Endothelial Cells.International journal of molecular sciences · 2019Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Increased microvascular dilatation and permeability is observed during allograft rejection. Because vascular integrity is an important indicator of transplant health, we have sought to limit injury to blood vessels by blocking complement activation. Although complement component 3 (C3) inhibition is known to be vasculoprotective in transplantation studies, we recently demonstrated the paradoxical finding that, early in rejection, C3(-/-) transplant recipients actually exhibit worse microvascular injury than controls. In the genetic absence of C3, thrombin-mediated complement component 5 (C5) convertase activity leads to the generation of C5a (anaphylatoxin), a promoter of vasodilatation and permeability. In the current study, we demonstrated that microvessel thrombin deposition is significantly increased in C3(-/-) recipients during acute rejection. Thrombin colocalization with microvessels is closely associated with remarkably elevated plasma levels of C5a, vasodilatation, and increased vascular permeability. Administration of NOX-D19, a specific C5a inhibitor, to C3(-/-) recipients of airway transplants significantly improved tissue oxygenation, limited microvascular leakiness, and prevented airway ischemia, even in the absence of conventional T-cell-directed immunosuppression. As C3 inhibitors enter the clinics, the simultaneous targeting of this thrombin-mediated complement activation pathway and/or C5a itself may confer significant clinical benefit.
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