ArticleThe Journal of clinical investigation2017
A C3(H20) recycling pathway is a component of the intracellular complement system.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
73 citing papers in PubMed, 1 synthesis or guideline pooled it, 110 citations in OpenAlex.
- Pitfalls in complement analysis: A systematic literature review of assessing complement activation.Frontiers in immunology · 2022Pooled it
- Article
- Intracellular complement Factor H promotes tumor progression through modulation of cell cycle and actin cytoskeleton.Communications biology · 2026Article
- The insider's perspective: The intracellular complosome and immune cell dynamics in cancer.Clinical and translational medicine · 2026Review
- Beta-cell-specific C3 deficiency exacerbates metabolic dysregulation and insulin resistance in obesity.Molecular metabolism · 2026Article
- The role of the complement system in gastrointestinal-related diseases.Frontiers in immunology · 2026Review
- Inside job: Roles of intracellular C3.The Journal of allergy and clinical immunology · 2025Review
- The secret life of complement: challenges and opportunities in exploring functions of the complosome in disease.The Journal of clinical investigation · 2025Review
- Cryo-EM analysis of complement C3 reveals a reversible major opening of the macroglobulin ring.Nature structural & molecular biology · 2025Article
- Native C3 is activated without proteolytic cleavage by transformation to C3(HFrontiers in immunology · 2025Article
- The role of complement in normal pregnancy and preeclampsia.Frontiers in immunology · 2025Review
- Canonical and non-canonical roles of complement in atherosclerosis.Nature reviews. Cardiology · 2024Review
- Local complement activation and modulation in mucosal immunity.Mucosal immunology · 2024Review
- Is the Complement System Dysregulated in Preeclampsia Comorbid with HIV Infection?International journal of molecular sciences · 2024Review
- Intracellular C3 protects β-cells from IL-1β-driven cytotoxicity via interaction with Fyn-related kinase.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A guide to complement biology, pathology and therapeutic opportunity.Nature reviews. Immunology · 2024Review
- Complement, complosome, and complotype: A perspective.European journal of immunology · 2023Review
- Complement System and the Kidney: Its Role in Renal Diseases, Kidney Transplantation and Renal Cell Carcinoma.International journal of molecular sciences · 2023Review
- Article
- Cell-autonomous regulation of complement C3 by factor H limits macrophage efferocytosis and exacerbates atherosclerosis.Immunity · 2023Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
An intracellular complement system (ICS) has recently been described in immune and nonimmune human cells. This system can be activated in a convertase-independent manner from intracellular stores of the complement component C3. The source of these stores has not been rigorously investigated. In the present study, Western blotting identified a band corresponding to C3 in freshly isolated human peripheral blood cells that was absent in corresponding cell lines. One difference between native cells and cell lines was the time absent from a fluid-phase complement source; therefore, we hypothesized that loading C3 from plasma was a route of establishing intracellular C3 stores. We found that many types of human cells specifically internalized C3(H2O), the hydrolytic product of C3, and not native C3, from the extracellular milieu. Uptake was rapid, saturable, and sensitive to competition with unlabeled C3(H2O), indicating a specific mechanism of loading. Under steady-state conditions, approximately 80% of incorporated C3(H2O) was returned to the extracellular space. These studies identify an ICS recycling pathway for C3(H2O). The loaded C3(H2O) represents a source of C3a, and its uptake altered the cytokine profile of activated CD4+ T cells. Importantly, these results indicate that the impact of soluble plasma factors should be considered when performing in vitro studies assessing cellular immune function.
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What OpenQuestion holds
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.