ArticleThe Journal of clinical investigation2005
Targeted complement inhibition by C3d recognition ameliorates tissue injury without apparent increase in susceptibility to infection.
Article in The Journal of clinical investigation, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.
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Who cites it
103 citing papers in PubMed, 193 citations in OpenAlex.
- Site-targeted proximal complement C3 inhibition, but not C5 blockade, attenuates neurodegeneration in a mouse model of amyotrophic lateral sclerosis: Implications for failed clinical trials.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- CR2-fH, A Targeted Inhibitor of Alternative Complement Pathway Reduces Dry AMD-Like Phenotype in AMD Patient iPSC-derived RPE Cells.Investigative ophthalmology & visual science · 2026Article
- Review
- Complement Modulation Mitigates Inflammation-Mediated Preterm Birth and Fetal Neural Inflammation.Cells · 2025Article
- Identifying Therapeutic Targets and Potential Drugs for Diabetic Retinopathy: Focus on Oxidative Stress and Immune Infiltration.Journal of inflammation research · 2025Article
- Article
- Canonical and non-canonical roles of complement in atherosclerosis.Nature reviews. Cardiology · 2024Review
- Local complement activation and modulation in mucosal immunity.Mucosal immunology · 2024Review
- Complement propagates visual system pathology following traumatic brain injury.Journal of neuroinflammation · 2024Article
- Sphingolipid metabolism and complement signaling in cancer progression.Trends in cancer · 2023Article
- Inhibition of complement C3 signaling ameliorates locomotor and visual dysfunction in autoimmune inflammatory diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Complement Drives Chronic Inflammation and Progressive Hydrocephalus in Murine Neonatal Germinal Matrix Hemorrhage.International journal of molecular sciences · 2023Article
- Mass cytometric analysis of the immune cell landscape after traumatic brain injury elucidates the role of complement and complement receptors in neurologic outcomes.Acta neuropathologica communications · 2023Article
- Complement as a vital nexus of the pathobiological connectome for acute respiratory distress syndrome: An emerging therapeutic target.Frontiers in immunology · 2023Review
- Complement Component 5 (C5) Deficiency Improves Cognitive Outcome After Traumatic Brain Injury and Enhances Treatment Effects of Complement Inhibitors C1-Inh and CR2-Crry in a Mouse Model.Neurotrauma reports · 2023Article
- A Role of Complement in the Pathogenic Sequelae of Mouse Neonatal Germinal Matrix Hemorrhage.International journal of molecular sciences · 2022Article
- Increasing the efficacy and safety of a human complement inhibitor for treating post-transplant cardiac ischemia reperfusion injury by targeting to a graft-specific neoepitope.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2021Article
- Chronic complement dysregulation drives neuroinflammation after traumatic brain injury: a transcriptomic study.Acta neuropathologica communications · 2021Article
- A novel injury site-natural antibody targeted complement inhibitor protects against lung transplant injury.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2021Article
- Natural immunoglobulin M-based delivery of a complement alternative pathway inhibitor in mouse models of retinal degeneration.Experimental eye research · 2021Article
43 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Previous studies indicate a pivotal role for complement in mediating both local and remote injury following ischemia and reperfusion of the intestine. Here, we report on the use of a mouse model of intestinal ischemia/reperfusion injury to investigate the strategy of targeting complement inhibition to sites of complement activation by linking an iC3b/C3dg-binding fragment of mouse complement receptor 2 (CR2) to a mouse complement-inhibitory protein, Crry. We show that the novel CR2-Crry fusion protein targets sites of local and remote (lung) complement activation following intestinal ischemia and reperfusion injury and that CR2-Crry requires a 10-fold lower dose than its systemic counterpart, Crry-Ig, to provide equivalent protection from both local and remote injury. CR2-Crry has a significantly shorter serum half-life than Crry-Ig and, unlike Crry-Ig, had no significant effect on serum complement activity at minimum effective therapeutic doses. Furthermore, the minimum effective dose of Crry-Ig significantly enhanced susceptibility to infection in a mouse model of acute septic peritonitis, whereas the effect of CR2-Crry on susceptibility to infection was indistinguishable from that of PBS control. Thus, compared with systemic inhibition, CR2-mediated targeting of a complement inhibitor of activation improved bioavailability, significantly enhanced efficacy, and maintained host resistance to infection.
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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.