ReviewImmunological reviews2016
Evolution of the complement system: from defense of the single cell to guardian of the intravascular space.
Review in Immunological reviews, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
76 citing papers in PubMed, 1 synthesis or guideline pooled it, 127 citations in OpenAlex.
- Novel evidence for complement system activation in chick myopia and hyperopia models: a meta-analysis of transcriptome datasets.Scientific reports · 2017Pooled it
- The neuroimmune system and cognition.Nature immunology · 2026Review
- Effect of complement 3/5 knockout on renal proteomics landscape after ischemia and reperfusion injury in rats.Physiological reports · 2026Article
- Cellular and molecular interactions underlying the peripheral immune responses to blood-stage malaria infections.ImmunoHorizons · 2026Review
- C3 inFrontiers in cellular and infection microbiology · 2026Article
- The complement cascade in Alzheimer's disease: modern implications of an ancient immune protagonist.Molecular neurodegeneration · 2025Review
- Inhibitory pattern recognition receptors: lessons from LAIR1.Nature reviews. Immunology · 2025Review
- A Lifelong Journey in the Field of the Pulmonary Circulation: Perspectives Through the Lens of the Cardiovascular Pulmonary Research Laboratory.Pulmonary circulation · 2025Article
- Emerging roles for complement in lung transplantation.The Journal of clinical investigation · 2025Review
- Targeting the complement-mTOR-autophagy axis: the role of apolipoprotein E in depression.BMC biology · 2025Article
- Friend or foe: assessing the value of animal models for facilitating clinical breakthroughs in complement research.The Journal of clinical investigation · 2025Review
- Knowing the enemy: strategic targeting of complement to treat Alzheimer disease.Nature reviews. Neurology · 2025Review
- CTSL-2 upon specifically recognizing Vibrio splendidus directly cleaves complement C3 to promote the bacterial phagocytosis and degradation in oyster.Cell communication and signaling : CCS · 2025Article
- Complement Factor B Deficiency Is Dispensable for Female Fertility but Affects Microbiome Diversity and Complement Activity.International journal of molecular sciences · 2025Article
- The Complement System.Advances in experimental medicine and biology · 2025Review
- Review
- Hemostasis and complement in allogeneic hematopoietic stem cell transplantation: clinical significance of two interactive systems.Bone marrow transplantation · 2024Review
- Local complement activation and modulation in mucosal immunity.Mucosal immunology · 2024Review
- The Role of the Complement System in Synaptic Pruning after Stroke.Aging and disease · 2024Review
- A guide to complement biology, pathology and therapeutic opportunity.Nature reviews. Immunology · 2024Review
16 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
3 authors at 1 institution in 1 country.
Funding
Abstract
The complement system is an evolutionarily ancient component of immunity that revolves around the central component C3. With the recent description of intracellular C3 stores in many types of human cells, our view of the complement system has expanded. In this article, we hypothesize that a primitive version of C3 comprised the first element of the original complement system and initially functioned intracellularly and on the membrane of single-celled organisms. With increasing specialization and multicellularity, C3 evolved a secretory capacity that allowed it to play a protective role in the interstitial space. Upon development of a pumped circulatory system, C3 was synthesized in large amounts and secreted by the liver to protect the intravascular space. Recent discoveries of intracellular C3 activation, a C3-based recycling pathway and C3 being a driver and programmer of cell metabolism suggest that the complement system utilizes C3 to guard not only extracellular but also the intracellular environment. We predict that the major functions of C3 in all four locations (i.e. intracellular, membrane, interstitium and circulation) are similar: opsonization, membrane perturbation, triggering inflammation, and metabolic reprogramming.
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Identifiers
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.