Affinage

Showing C3 — C3B is a alias.

C3

Complement C3 · UniProt P01024

Length
1663 aa
Mass
187.1 kDa
Annotated
2026-06-09
100 papers in source corpus 49 papers cited in narrative 49 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/8 claims corpus-supported (88%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

C3 is the central hub of the complement system, undergoing proteolytic activation that simultaneously deposits an opsonin on target surfaces and releases a diffusible inflammatory mediator (PMID:6903192). Native C3 contains a buried thioester bond that, upon cleavage to C3b, is exposed and displaced >85 Å by massive domain rearrangements across its 12 domains, presenting a reactive carbonyl for covalent ester-bond attachment to target hydroxyl groups and exposing cryptic binding sites for factor B and complement regulators (PMID:6903192, PMID:17051160). C3b nucleates the alternative-pathway C3 convertase (C3b,Bb), a metal-dependent complex stabilized by properdin, which prolongs convertase half-life up to 10-fold (PMID:1185108, PMID:6553050). This amplification loop is restrained by regulators that drive C3b inactivation: factor H (beta1H) and C4BP act as cofactors and decay accelerators, factor I (C3bINA) cleaves the C3b alpha-chain to iC3b, and the Sez6 family provides both decay-accelerating and factor I cofactor activity, while disease-associated C3 mutation R139W generates a hyperactive convertase resistant to such control (PMID:448074, PMID:293746, PMID:22246034, PMID:18684951, PMID:33936031). The opsonin products are recognized by distinct cellular receptors: clustered C3b receptors mediate adsorptive endocytosis and, with iC3b receptors, support phagocytosis activated by trans-membrane signals, while CR3-mediated recognition of iC3b directs microglial clearance of apoptotic cells (PMID:7252422, PMID:7153708, PMID:6225825, PMID:31209071). The released C3a anaphylatoxin requires an intact C-terminal arginine for activity and signals through the Gi-coupled C3aR, with C5L2/GPR77 acting as a positive modulator; C3a desArg fails to bind C3aR despite a conserved structure, establishing that this loss is not conformational (PMID:803505, PMID:17322907, PMID:10232396, PMID:23184394). Through C3aR, C3a drives mast cell histamine release and chemotaxis, leukocyte and hematopoietic progenitor migration, and an expanding range of tissue responses including hepatocyte proliferation during liver regeneration, monocyte recruitment in muscle regeneration, post-ischemic neural plasticity via GAP43, VEGF-driven choroidal neovascularization, Th1 differentiation through AKT and IL-2 receptor assembly, and tubular/podocyte injury via AKT/β-catenin and mitochondrial cAMP pathways (PMID:9108406, PMID:12975457, PMID:15240660, PMID:12511407, PMID:24033923, PMID:27956400, PMID:29233958, PMID:16452172, PMID:32161193, PMID:30944246). Human C3 deficiency impairs Th1 but not Th2 responses, demonstrating a cell-autonomous role for T cell-derived C3a (PMID:24321396).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1975 High

    Established how the alternative-pathway convertase is kept active long enough to amplify, by showing properdin directly stabilizes the surface-bound C3b,Bb enzyme.

    Evidence Hemolytic assays on cellular intermediates with decay kinetics and cell-to-cell transfer

    PMID:1185108

    Open questions at the time
    • Did not define the structural basis of properdin binding to C3b
    • Did not address regulation under physiological surface conditions
  2. 1975 High

    Defined the structural requirement for C3a activity by showing the C-terminal arginine is essential for anaphylatoxin function.

    Evidence Purification of human/porcine C3a, carboxypeptidase treatment, smooth muscle and histamine bioassays

    PMID:803505

    Open questions at the time
    • Did not identify the C3a receptor
    • Did not explain why desArg loses activity at molecular level
  3. 1979 High

    Defined complement regulation of C3b by showing factor I plus factor H (beta1H) and C4BP cleave/decay C3 and C4 convertases to terminate amplification.

    Evidence Reconstituted hemolytic and convertase assays with purified regulators and SDS-PAGE of cleavage fragments

    PMID:293746 PMID:448074

    Open questions at the time
    • Did not resolve the structural sites of regulator binding
    • Did not order cofactor versus decay-accelerating contributions in vivo
  4. 1980 High

    Identified the thioester bond as the chemical basis for covalent C3b surface attachment and convertase formation, the founding mechanism of opsonization.

    Evidence Radiolabeled methylamine modification with hemolytic and convertase assays and zymosan binding

    PMID:6903192

    Open questions at the time
    • Did not visualize the conformational change accompanying activation
    • Did not define receptor recognition of the deposited fragment
  5. 1983 High

    Showed the alternative-pathway convertase is a defined metal-dependent stable complex, explaining its catalytic requirements.

    Evidence Sucrose gradient sedimentation, radiolabeled Ni2+ stoichiometry, and EDTA chelation

    PMID:6553050

    Open questions at the time
    • Did not place the metal site at residue resolution
    • Did not connect metal dependence to regulator action
  6. 1983 High

    Demonstrated non-canonical proteases (mast cell tryptase) can generate C3a, broadening the routes of anaphylatoxin production.

    Evidence In vitro tryptase cleavage of purified C3 with SDS-PAGE, RIA, and ileum bioassay

    PMID:6339618

    Open questions at the time
    • Did not establish in vivo relevance of tryptase-generated C3a
    • Did not identify the receptor mediating the activity
  7. 1983 High

    Mapped C3b/iC3b receptor function on phagocytes, distinguishing attachment from activated ingestion and showing trans-membrane signaling controls phagocytic competence.

    Evidence Receptor internalization assays, PMA activation, and substrate-bound fibronectin/SAP phagocytosis assays in monocytes

    PMID:6225825 PMID:7153708 PMID:7252422

    Open questions at the time
    • Did not molecularly identify the receptors
    • Did not define the signaling intermediates of the trans-membrane signal
  8. 1997 Medium

    Linked C3a to Gi-coupled signaling by demonstrating pertussis-toxin-sensitive chemotaxis and calcium mobilization in mast cells.

    Evidence Boyden chamber chemotaxis with laminin dependence, pertussis toxin inhibition, and Ca2+ imaging

    PMID:7513741 PMID:9108406

    Open questions at the time
    • Single lab characterization
    • Did not clone or directly identify the receptor protein
  9. 1999 High

    Established C3aR ligand specificity, showing C3a but not C3a desArg binds and signals, with autocrine C3a loops operating in renal tubular cells.

    Evidence Binding and functional assays in C3aR-transfected RBL-2H3 cells; autocrine signaling readouts in HK-2 cells

    PMID:10232396 PMID:10571781

    Open questions at the time
    • Did not explain the molecular basis of desArg inactivity
    • Autocrine renal loop confined to single cell-line study
  10. 2000 High

    Demonstrated C3aR as a physiological effector pathway in disease using genetic knockouts in asthma and demonstrating human C3a generation after allergen challenge.

    Evidence C3aR knockout mice in allergen models with human BAL C3a measurement

    PMID:10984054

    Open questions at the time
    • Did not define the cellular source of C3a in airway
    • Did not resolve downstream signaling effectors
  11. 2003 High

    Extended C3a/C3aR signaling beyond inflammation to tissue regeneration and progenitor mobilization.

    Evidence Partial hepatectomy and CCl4 injury in C3-/-/C3aR-/- mice with reconstitution; CD34+ progenitor chemotaxis and engraftment assays

    PMID:12511407 PMID:12975457 PMID:15240660

    Open questions at the time
    • Did not fully define proliferative signaling intermediates
    • Did not separate C3a from C5a contributions in all readouts
  12. 2006 High

    Provided the structural basis for activation, showing C3-to-C3b conversion drives large domain rearrangements that expose the thioester and cryptic binding sites.

    Evidence X-ray crystallography of C3b at 4 Å

    PMID:17051160

    Open questions at the time
    • Limited 4 Å resolution
    • Did not capture regulator-bound complexes
  13. 2007 High

    Identified C5L2/GPR77 as a positive modulator of C3a (and C5a) signaling, expanding the receptor framework for anaphylatoxin responses.

    Evidence C5L2 gene targeting with in vitro signaling and in vivo LPS/airway models

    PMID:17322907

    Open questions at the time
    • Did not resolve molecular mechanism of co-receptor modulation
    • Did not define direct C3a binding to C5L2
  14. 2011 High

    Revealed a developmental role for C3a/C3aR in mediating coattraction during collective neural crest migration.

    Evidence Xenopus neural crest morpholino knockdown with recombinant C3a rescue and live imaging

    PMID:22118769

    Open questions at the time
    • Did not define the downstream cytoskeletal effectors of coattraction
    • Mammalian developmental relevance not addressed
  15. 2012 High

    Resolved that C3a desArg inactivity is not conformational and linked a disease mutation to convertase hyperactivity.

    Evidence Crystal structures of C3a and C3a desArg; SPR and convertase assays of aHUS R139W mutant C3

    PMID:22246034 PMID:23184394

    Open questions at the time
    • Did not define how the C-terminal arginine engages C3aR
    • R139W studied in a single in vitro system
  16. 2016 High

    Established C3a/C3aR as a driver of post-injury tissue remodeling across neural, muscle, fibrotic, and cardiac contexts.

    Evidence Stroke, cardiotoxin muscle injury, nephropathy, and pulmonary artery banding models in C3/C3aR knockouts with pharmacological blockade

    PMID:19158354 PMID:27956400 PMID:29233958 PMID:36109509

    Open questions at the time
    • Cellular source of C3a varies and is not uniformly defined
    • Downstream pathways differ by tissue and are incompletely connected
  17. 2020 High

    Defined intracellular signaling pathways downstream of C3aR in renal injury, including AKT/β-catenin transcriptional and mitochondrial cAMP routes.

    Evidence In vitro podocyte/tubular C3a stimulation and in vivo C3aR antagonist nephropathy models with mitochondrial and transcriptional readouts

    PMID:30944246 PMID:32161193 PMID:35777783

    Open questions at the time
    • Did not establish direct receptor-to-effector molecular coupling
    • Effects largely characterized within single laboratories

Open questions

Synthesis pass · forward-looking unresolved questions
  • How C3a's C-terminal arginine engages C3aR to trigger signaling, and how tissue-specific C3aR effector pathways are selected, remain unresolved.
  • No receptor-ligand co-structure of C3a bound to C3aR
  • Mechanism selecting AKT/β-catenin versus cAMP versus Rho outputs across tissues is unknown
  • Role of C5L2 in modulating C3a output not mechanistically defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 6 GO:0060089 molecular transducer activity 4 GO:0098772 molecular function regulator activity 4
Localization
GO:0005576 extracellular region 4 GO:0005886 plasma membrane 3
Pathway
R-HSA-168256 Immune System 6 R-HSA-1266738 Developmental Biology 5 R-HSA-162582 Signal Transduction 5 R-HSA-1643685 Disease 5
Partners
C3AR1C4BPCFBCFHCFICFPCR3GPR77
Complex memberships
C3 convertase (C3b,Bb)classical C3 convertase (C4b2a)

Evidence

Reading pass · 49 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1980 Native C3 contains a thioester bond (active carbonyl group) that, upon enzymatic cleavage to C3b, enables covalent ester-bond attachment to hydroxyl groups on target surfaces; methylamine modification of native C3 mimics C3b function by reacting with the thioester, exposing a sulfhydryl group in the C3d region and allowing factor B binding and alternative-pathway C3 convertase formation without proteolysis. Radiolabeled methylamine/iodoacetamide incorporation, hemolytic activity assays, convertase formation assay with purified factors B and D, anti-C3a antibody inhibition, zymosan particle binding experiments The Journal of experimental medicine High 6903192
1975 Properdin (P) binds directly to C3b on cell surfaces and stabilizes the alternative-pathway C3 convertase (C3bBb) by prolonging its half-life up to 10-fold in a dose-dependent manner, without increasing the number of convertase sites; P can transfer between convertase sites carrying its stabilizing activity. Hemolytic assay with EAC43B intermediates, dose-response decay kinetics, temperature-dependence binding studies, cell-to-cell transfer experiments The Journal of experimental medicine High 1185108
1979 C3b inactivator (C3bINA) together with cofactor beta1H cleaves the alpha-chain of cell-bound C3b into two fragments (C3b-alpha-60 and C3b-alpha-40, held together with the beta-chain by disulfide bonds), generating C3b' (iC3b); this conversion abolishes immune adherence to erythrocytes and the ability to form the amplification C3 convertase, while leaving C3c and C3d antigenic sites intact; trypsin further releases C3b' fragments leaving a 32 kDa C3d-bearing fragment covalently linked to the membrane. SDS-PAGE analysis of cell-bound C3b fragments, immune adherence assay, convertase formation assay, trypsin cleavage, anti-C3c/anti-C3d agglutination Journal of immunology High 448074
1979 C4 binding protein (C4BP) inhibits assembly and accelerates decay of the classical-pathway C3 convertase (C4b2a) by displacing C2a from C4b binding sites; C4BP also enhances C3b inactivator-mediated cleavage of cell-bound C4b alpha'-chain; removal of C4BP from serum promotes vigorous C3 consumption after C1 addition. Hemolytic assay with cellular intermediates (EAC14), immune absorption depletion of C4BP, reconstitution with purified C4BP, Tmax analysis Proceedings of the National Academy of Sciences of the United States of America High 293746
2006 Crystal structure of C3b at 4 Å resolution reveals that proteolytic activation of C3 to C3b causes massive domain rearrangements across its 12 domains; the thioester is fully exposed and displaced >85 Å from its buried location in native C3, and a new molecular surface is presented that exposes cryptic binding sites for factor B and complement regulators. X-ray crystallography at 4 Å resolution Nature High 17051160
1983 Mast cell tryptase cleaves only the alpha-chain of C3, generating C3a anaphylatoxin (identified by SDS-PAGE co-migration, radioimmunoassay, and guinea pig ileum bioassay); heparin co-released from mast cell granules enhances catabolism of the generated C3a by tryptase, thereby down-regulating C3a activity. In vitro enzymatic cleavage of purified C3 by tryptase, SDS-PAGE, radioimmunoassay for C3a, guinea pig ileum bioassay, heparin co-incubation experiment Journal of immunology High 6339618
1975 Purified human and porcine C3a anaphylatoxins require an intact C-terminal arginine residue for smooth muscle contraction and histamine release from mast cells; removal of the C-terminal arginine abolishes these activities. Both are generated by classical-pathway C4,2 enzyme and alternative-pathway enzymes with equal structure. Purification from inulin-activated serum, carboxypeptidase treatment, smooth muscle contraction bioassay, histamine release from mast cells, amino acid sequencing, SDS-PAGE The Journal of biological chemistry High 803505
1983 The alternative-pathway C3 convertase (C3b,Bb) is an active, stable complex with a sedimentation coefficient of 10.7 S containing one mole of metal ion (Ni2+ or Mg2+) per mole of complex; the metal ion is located in the Bb subunit and is required for enzyme activity; Ni2+ binds more tightly than Mg2+ to the same site, explaining the enhanced stability of the Ni2+-containing convertase. Sucrose density gradient ultracentrifugation, enzymatic activity assay, 63Ni2+ radiolabeling, EDTA chelation, metal displacement experiments The Journal of biological chemistry High 6553050
1981 C3b receptors on PMN are non-randomly distributed in small clusters and undergo adsorptive endocytosis via a multivalency-dependent mechanism (bivalent but not monovalent anti-receptor antibody, or cross-linked C3b-opsonized targets trigger internalization); internalized receptor-ligand complexes become inaccessible to surface probes within 10 minutes at 37°C. Indirect immunofluorescence with mono/bivalent anti-C3b receptor antibodies, 125I/131I dual radiolabeling endocytosis assay, pronase surface accessibility assay, cross-linking with F(ab')2 anti-C3 The Journal of experimental medicine High 7252422
1982 C3b and C3b' (iC3b) receptors on human monocytes mediate attachment but not ingestion of opsonized erythrocytes in resting cells; phorbol esters (PMA) activate phagocytosis specifically through these C3 receptors in a cycloheximide-insensitive, colchicine-sensitive manner that develops after 3 days of culture; the two receptor types function independently. Percoll gradient monocyte isolation, erythrocyte rosette/phagocytosis assay with C3b- and C3b'-coated particles, PMA treatment, competitive plating on C3b/C3b'-coated surfaces The Journal of experimental medicine High 7153708
1983 Substrate-bound (but not soluble) fibronectin and serum amyloid P component activate C3b and C3bi receptor-mediated phagocytosis in cultured human monocytes via a trans-membrane signal; activation of receptors on the basal surface propagates to apical surface C3 receptors at remote sites. Phagocytosis assay with C3b/C3bi-coated erythrocytes, soluble vs. substrate-bound fibronectin comparison, apical/basal surface receptor activity measurement The Journal of experimental medicine Medium 6225825
1983 C3a (but not C3a desArg) activates human platelets to aggregate and release serotonin; C3a desArg retains platelet-stimulating activity equal to intact C3a despite loss of anaphylatoxin (smooth muscle) activity, suggesting the platelet-stimulating site and anaphylatoxin site are distinct; ultrastructural evidence shows C3a binding to platelet membranes. Platelet aggregation assay with gel-filtered platelets, serotonin release assay, ADP synergism assay, electron microscopy with anti-C3a immunostaining The Journal of experimental medicine Medium 6604123
1997 C3a and C5a are chemotactic for human mast cells (HMC-1, cord blood-derived, cutaneous) in a dose-dependent, pertussis-toxin-sensitive manner requiring an extracellular matrix (laminin); C3a and C5a also mobilize intracellular calcium in HMC-1 cells, indicating Gi protein-coupled receptor signaling. Modified Boyden chamber chemotaxis assay, laminin dependence experiment, pertussis toxin inhibition, intracellular Ca2+ imaging Blood Medium 9108406
1994 C3a and C5a release histamine from human skin mast cells; the C-terminal arginine of both peptides is required for this activity; release is non-cytotoxic, independent of extracellular calcium, and complete within 15 seconds; C3a and C5a act through a site distinct from substance P. Histamine release assay from dispersed skin mast cells, carboxypeptidase treatment, metabolic inhibitor controls, substance P antagonist comparison, time-course studies The Journal of investigative dermatology Medium 7513741
2003 C3a and C5a are required for liver regeneration after partial hepatectomy; lack of C3 and C5a receptor signaling attenuates NF-κB/STAT-3 activation and IL-6/TNFα induction post-hepatectomy; reconstitution of C3- and C5-deficient mice with exogenous C3a and C5a rescues the regeneration defect. Partial hepatectomy in C3-/- and C5-/- mice, genetic reconstitution with recombinant C3a/C5a, NF-κB/STAT-3 activation assay, cytokine measurement The Journal of experimental medicine High 12975457
2004 C3a promotes hepatocyte proliferation via the C3a receptor (C3aR) during liver regeneration after CCl4 injury; two waves of complement activation occur; early C3a generation primes hepatocytes for S-phase entry; C3aR-deficient mice show impaired hepatocyte proliferation; C3a reconstitution of C3-/- mice restores proliferative capacity. CCl4 liver injury model, C3-/- and C3aR-/- mice, cobra venom factor decomplementation, BrdU incorporation (S-phase entry), serum C3a RIA, C3a reconstitution Journal of immunology High 15240660
2000 Genetic deletion of C3a receptor (C3aR) in mice protects against allergen-induced changes in lung physiology in a murine asthma model; human asthmatics generate significant C3a following intra-pulmonary allergen (but not saline) deposition, establishing C3aR-mediated signaling as an effector pathway in asthma. C3aR knockout mice, allergen challenge model, lung physiology measurements, C3a ELISA in human BAL fluid Nature High 10984054
2002 C3a and C5a from drusen induce VEGF expression in retinal pigment epithelium in vitro and in vivo; genetic ablation of C3aR or C5aR reduces VEGF expression, leukocyte recruitment, and choroidal neovascularization after laser injury; antibody-mediated neutralization or pharmacological receptor blockade also reduces CNV. In vitro VEGF induction assay, laser-induced CNV mouse model, C3aR/C5aR knockout mice, antibody neutralization, receptor antagonist pharmacology Proceedings of the National Academy of Sciences of the United States of America High 16452172
2011 Complement fragment C3a mediates mutual cell-cell attraction (coattraction) of migrating neural crest cells via C3aR; C3a/C3aR-dependent coattraction maintains cohesive clusters during collective migration by counterbalancing contact inhibition of locomotion; loss of C3aR disrupts collective and coordinated neural crest cell movements. Xenopus neural crest cell migration assay, C3aR loss-of-function (morpholino knockdown), rescue with recombinant C3a, live imaging of collective migration Developmental cell High 22118769
2007 C5L2 (GPR77) functions as a positive modulator of both C5a- and C3a-induced signaling in neutrophils, macrophages, and fibroblasts; C5L2-deficient mice phenocopy C3aR-deficient mice in hypersensitivity to LPS-induced septic shock and reduced OVA-induced airway hyper-responsiveness. Gene targeting (C5L2 knockout), in vitro C3a/C5a signaling assays in primary cells, LPS challenge model, OVA airway model Nature High 17322907
2003 Normal human CD34+ hematopoietic stem/progenitor cells express functional C3aR and respond to C3a with calcium flux; C3a potentiates SDF-1 (CXCL12)-dependent chemotaxis, trans-Matrigel migration, MMP-9 secretion, and VLA-4-mediated adhesion to VCAM-1; bone marrow stroma secretes C3; C3a-primed murine Sca-1+ cells engraft faster in vivo. Flow cytometry (C3aR expression), calcium flux assay, transwell chemotaxis assay, trans-Matrigel migration, MMP-9 ELISA, VCAM-1 adhesion assay, in vivo engraftment model Blood High 12511407
2002 C3a and C5a induce distinct signal transduction cascades in endothelial cells: C3aR activation causes transient actin stress fiber formation via Rho (G-alpha12/13-dependent, pertussis toxin-insensitive); C5aR activation causes delayed cytoskeletal retraction and increased paracellular permeability via PI3K/src/EGFR transactivation (pertussis toxin-sensitive). Actin stress fiber assay, pertussis toxin inhibition, rho activation assay, paracellular permeability assay, EGFR phosphorylation immunoprecipitation, pharmacological inhibitors (PI3K, src, EGFR) Journal of immunology Medium 12165538
2012 The aHUS-associated C3 mutation R139W creates a hyperactive C3 convertase; mutant C3 shows increased affinity for factor B and reduced binding to MCP (CD46) but normal regulation by factor H, leading to increased C3 deposition and C5a release on inflamed glomerular endothelial cells. C3 deposition and C5a ELISA on glomerular endothelial cells, SPR binding assays for factor B, MCP, factor H interactions, C3 convertase activity assay with mutant vs wild-type C3 Blood High 22246034
2008 Factor H contains distinct binding sites for C3b and glycosaminoglycans: CCP 1–4 (Kd ~14 µM) and CCPs 19–20 (Kd ~3.5 µM) bind C3b; CCPs 7–8 and 19–20 bind heparin; previously reported CCPs 8–9, 12–13 heparin-binding activity was artifactual; none of CCPs 9–15 show significant C3b binding. Recombinant CCP module expression, heparin-affinity chromatography, gel-mobility shift assays, SPR (surface plasmon resonance) with C3b on CM5 and C1 chips Journal of immunology High 18684951
1996 C3a modulates LPS-induced TNF-alpha and IL-1beta synthesis in PBMCs in a cell-context-dependent manner: C3a suppresses cytokine production in non-adherent (circulating) PBMCs but enhances it in adherent (tissue-resident) PBMCs at the mRNA level; these effects are independent of PGE2 and are shared by C3a desArg. PBMC culture (adherent vs non-adherent), ELISA for TNF-alpha/IL-1beta, Northern blot for mRNA, indomethacin PGE2 blockade Journal of immunology Medium 8617973
1999 HK-2 proximal tubular cells produce C3a, C3, and factors B and H via the alternative complement pathway; locally generated C3a signals back through the C3aR on HK-2 cells via a pertussis toxin-sensitive (Gi) pathway, inducing inositol phosphate production, tyrosine phosphorylation of at least two proteins, and TGF-beta1 secretion. RT-PCR for alternative pathway mRNAs, Western blot for secreted C3a, C3a RIA, inositol phosphate assay, pertussis toxin inhibition, TGF-beta1 ELISA, tyrosine phosphorylation Western blot Kidney international Medium 10571781
1999 C3a(desArg) does not bind to the C3a receptor and does not signal through it; recombinant C3a binds C3aR with half-maximal concentration ~3 nM while rC3a(desArg) shows no detectable binding; C3aR-expressing RBL-2H3 transfectants respond to C3a but not C3a(desArg) for enzyme release and chemotaxis. Flow cytometry binding assay on C3aR-transfected RBL-2H3 cells with His-tagged ligands, N-acetyl-beta-D-glucosaminidase release assay, Boyden chamber chemotaxis assay Immunology letters High 10232396
2012 Human C3a and C3a desArg have conserved three-dimensional structures (crystal structures at 2.3 and 2.6 Å, respectively) with no significant conformational differences, in contrast to C5a/C5a desArg; the loss of C3aR signaling by C3a desArg is therefore not due to a conformational change upon C-terminal arginine removal. Recombinant protein expression and purification, X-ray crystallography at 2.3 Å (C3a) and 2.6 Å (C3a desArg) Protein science High 23184394
1998 C3a enhances LPS-induced NF-κB and AP-1 binding and IL-6 synthesis in adherent PBMCs while suppressing it in non-adherent PBMCs; both effects are mediated through a Gi protein-coupled pathway (blocked by pertussis toxin) and are independent of PGE2; C3a desArg shares these immunomodulatory effects. NF-κB/AP-1 gel mobility shift assay, IL-6 ELISA and Northern blot, pertussis toxin inhibition, indomethacin control Journal of immunology Medium 9886419
2012 S. aureus proteins Sbi and Efb simultaneously bind C3/C3b and plasminogen; bound plasminogen is converted to plasmin by staphylokinase or urokinase, which then degrades complement C3, C3b, and C3a; Sbi and Efb enhance plasmin-mediated C3/C3b cleavage by inducing conformational changes in C3/C3b. Co-immunoprecipitation/pulldown of Sbi/Efb with C3 and plasminogen, in vitro plasmin cleavage assay of C3/C3b, SDS-PAGE of degradation products PloS one Medium 23071827
2010 C3a binds to RAGE (receptor for advanced glycation end products) with EC50 ~1.9 nM; CpG oligonucleotides also bind RAGE directly and form a ternary complex with C3a/RAGE, increasing binding affinity to EC50 ~70 pM; C3a synergizes with CpG to increase IFN-alpha production from PBMCs in a RAGE-dependent manner. ELISA binding assay, SPR, fluorescence anisotropy, neutralizing anti-RAGE antibody and soluble RAGE inhibition, IFN-alpha ELISA, RAGE-/- mouse bone marrow cell assay Journal of immunology Medium 20817881
2013 Human T cells and dendritic cells locally produce C3a and C5a during allogeneic responses; both cell types express C3aR and C5aR; C3aR/C5aR antagonists inhibit T cell proliferation; recombinant C3a promotes CD4+ T cell expansion and induces AKT phosphorylation; siRNA knockdown of DC C3 reduces T cell alloresponses; downregulation of DAF increases local C3a/C5a and augments T cell proliferation. C3a/C5a ELISA in T cell cultures, C3aR/C5aR antagonist treatment, recombinant C3a stimulation, AKT phosphorylation Western blot, siRNA knockdown of DC C3, DAF knockdown, in vivo GVHD NOD scid mouse model American journal of transplantation High 24033923
2009 C3a mediates epithelial-to-mesenchymal transition (EMT) in tubular epithelial cells; C3a exposure reduces E-cadherin and increases alpha-smooth muscle actin and collagen I expression; C3aR antagonist blocks both C3a-induced and serum-induced EMT; C3aR-deficient mice show less renal interstitial fibrosis in the adriamycin nephropathy model. In vitro C3a stimulation of tubular cells, E-cadherin/alpha-SMA/collagen I expression by Western blot and qPCR, C3aR antagonist (SB290157), C3aR-/- mice in adriamycin nephropathy model Journal of the American Society of Nephrology High 19158354
2016 C3a/C3aR signaling stimulates post-ischemic neural plasticity; C3a overexpression in astrocytes increases GAP43 expression (axonal sprouting marker) post-stroke; C3aR deficiency decreases GAP43; intranasal C3a treatment starting 7 days post-stroke increases synaptic density, GAP43, and accelerates functional recovery of forepaw motor function. Photothrombotic stroke model, C3aR-/- and GFAP-C3a transgenic mice, GAP43 immunostaining, synaptic density quantification, forepaw motor function behavioral testing, intranasal C3a administration Brain High 27956400
2017 Complement C3a signals via C3aR to regulate monocyte/macrophage recruitment during skeletal muscle regeneration; C3a/C3aR deficiency reduces expression of adhesion molecules, cytokines, and antigen-processing genes in monocytes; exogenous CCL5 rescues the recruitment defect in C3aR-deficient mice; the alternative pathway component Cfb is required upstream. Cardiotoxin-induced muscle injury model, C3-/-, Cfb-/-, C3aR-/- mice, monocyte gene expression profiling, immunohistochemistry for macrophage infiltration, recombinant CCL5 rescue experiment Nature communications High 29233958
2019 C3-dependent microglial clearance via CR3 (iC3b receptor) protects photoreceptors in retinitis pigmentosa; C3 activation localizes to activated microglia; genetic ablation of C3 or CR3 reduces microglial phagocytosis of apoptotic photoreceptors, increases microglial neurotoxicity, and accelerates photoreceptor degeneration. rd10 mouse model, C3-/- and CR3-/- genetic ablation, immunohistochemistry for complement components and microglia markers, photoreceptor degeneration quantification, microglial phagocytosis assay The Journal of experimental medicine High 31209071
2021 The Sez6 family (Sez6, Sez6L, Sez6L2) inhibits complement by: (1) accelerating C3 convertase dissociation (decay-accelerating activity) and (2) serving as cofactors for Factor I to cleave C3b; Sez6L2 has no cofactor activity for C4b; these activities specifically reduce C3b/iC3b opsonization via both classical and alternative pathways. Complement opsonization assay (C3b/iC3b deposition), convertase decay assay, Factor I cofactor assay with C3b and C4b substrates, SDS-PAGE of cleavage products Frontiers in immunology High 33936031
2005 C3a enhances CXCL12-induced chemotaxis of hematopoietic progenitor cells independently of the classical C3aR; C3a-desArg and C4a (but not C5a) share this activity; C3a directly interacts with CXCL12 and increases its binding affinity to CXCR4 on C3aR-negative cells; C3aR knockout BM cells respond normally to C3a/CXCL12 enhancement. Transwell chemotaxis assay, C3aR flow cytometry, SB290157 C3aR antagonist, C3aR-/- mouse BM cells, CXCL12-binding assay on CXCR4+/C3aR- REH cells Journal of immunology Medium 16148115
2005 The C3aR antagonist SB 290157 has full agonist activity on C3aR in multiple assay systems (calcium mobilization in C3aR-transfected RBL cells, beta-lactamase reporter in CHO-NFAT-bla cells, enzyme release from U-937 cells), but lacks agonist activity in cells expressing C3aR at very low levels (guinea pig platelets); results attributed to C3aR antagonism by SB 290157 in the literature may reflect agonist effects. Calcium mobilization assay in transfected RBL cells, beta-lactamase reporter assay in CHO-NFAT-bla cells, enzyme release from differentiated U-937 cells, guinea pig platelet assay Immunology letters Medium 16154494
2014 Cigarette smoke-induced neutrophil elastase cleaves C3 to release C3a, which increases C3aR expression on lung myeloid dendritic cells via autocrine/paracrine signaling; C3-/- and C3aR-/- mice develop less emphysema and have fewer lung mDC infiltrates after chronic smoke exposure. Chronic cigarette smoke model, C3-/- and C3aR-/- mice, neutrophil elastase C3 cleavage assay, lung mDC quantification, immunostaining for C3 deposits in human smoker tissue Mucosal immunology Medium 25465103
2022 C3a/C3aR activation induces podocyte injury in primary membranous nephropathy; C3aR blockade in Heymann nephritis rats reduces proteinuria, foot process effacement, and glomerular basement membrane thickening; human podocytes exposed to MN plasma show C3aR-dependent increases in PLA2R, Wnt3/β-catenin, and decreases in synaptopodin. Heymann nephritis rat model with C3aR antagonists (SB290157, JR14a), electron microscopy, proteinuria measurement, human podocyte in vitro stimulation with MN plasma, C3aR immunostaining Journal of the American Society of Nephrology High 35777783
2020 C3a/C3aR signaling induces mitochondrial fragmentation and dysfunction in podocytes via cAMP-dependent mechanisms; C3aR blockade normalizes mitochondrial morphology, SOD2 expression, and energetic metabolism and preserves podocyte density in diabetic nephropathy (BTBR ob/ob) mice. BTBR ob/ob mouse model with C3aR antagonist, electron microscopy of podocyte mitochondria, cAMP assay, SOD2 Western blot, in vitro podocyte C3a stimulation, mitochondrial membrane potential assay, SS-31 mitochondrial protector rescue JCI insight High 32161193
2022 The C3-complement factor D (Cfd)-C3aR axis drives right ventricular failure; C3 knockout attenuates right ventricular dysfunction and fibrosis; C3a is generated by the Cfd-containing C3 convertase complex; Cfd knockout also attenuates RV failure; C3aR antagonist dramatically improves right ventricular dysfunction in mice. Pulmonary artery banding mouse model, C3-/- mice, Cfd-/- mice, C3aR antagonist treatment, echocardiography, histological fibrosis quantification Nature communications High 36109509
2023 SARS-CoV-2 spike protein S1 activates the C3/C3aR pathway in lung endothelium in vivo; S1 injection in ACE2-transgenic mice induces C3 deposits, increased C3aR expression, thrombomodulin loss, and vWF increase followed by fibrin/platelet aggregates and fibrosis; C3aR antagonist inhibits lung C3 accumulation and limits thrombo-inflammation. S1 injection in hACE2 transgenic mice, C3aR antagonist treatment, immunofluorescence for C3/C3aR/thrombomodulin/vWF, lung histopathology Scientific reports Medium 37452090
1996 Adipose tissue activates the alternative complement pathway through local expression of C3, factor B, and adipsin/factor D, generating C3a/ASP (acylation stimulating protein); complement activation regulatory genes Crry and factor H are downregulated during adipocyte differentiation; plasma C3a levels correlate with plasma triglyceride levels in lean mice. RT-PCR for complement regulatory genes in preadipocytes vs adipocytes, murine C3a/ASP radioimmunoassay in lean vs obese mice, triglyceride correlation analysis Obesity research Medium 8946437
2019 C3a promotes versican V1 transcription in tubular cells via the AKT/β-catenin pathway; C3aR knockout in mice decreases versican expression in adriamycin nephropathy; tubular cell-derived versican V1 activates fibroblasts via CD44/Smad3 pathway; C3aR and suPAR/integrin β6 cooperate to increase versican V1 through transcriptional and splicing mechanisms respectively. C3a stimulation of tubular cells, AKT/β-catenin Western blot, C3aR-/- mice in ADR model, versican V1 quantification by qPCR/IHC, fibroblast co-culture assay JCI insight Medium 30944246
2006 C3a-derived peptides (including CNY21, residues Cys57-Arg77 of C3a) have antifungal activity against Candida by binding to cell surfaces and inducing membrane perturbations; arginine residues are critical for this antimicrobial activity; Candida infection induces complement degradation leading to C3a generation. Fluorescence and electron microscopy of Candida-peptide interactions, minimal inhibitory concentration assay, arginine-substitution variants, complement degradation assay in Candida-exposed serum Biochimica et biophysica acta Medium 17169328
2009 C3a and C5a sensitize cutaneous nociceptors: both fragments lower heat response thresholds and increase action potential firing in C-nociceptors; A-nociceptors are activated; C5aR mRNA is expressed in dorsal root ganglia; C3a and C5a elevate intracellular Ca2+ in DRG neurons and facilitate capsaicin-induced Ca2+ responses. In vivo intraplantar injection hyperalgesia model, skin-nerve in vitro preparation for nociceptor recording, DRG RT-PCR for C5aR, Ca2+ imaging in DRG neurons Pain Medium 20031321
2013 Normal Th1 induction in human T cells requires T cell-derived C3a and C3aR signaling; C3-deficient patient T cells show impaired Th1 but intact Th2 responses in vitro, phenocopying CD46-deficient patients; C3-deficient CD4+ T cells have reduced CD25 and CD122 expression, linking complement-derived C3a to IL-2 receptor assembly. T cells from C3-deficient patients, cytokine ELISA/FACS for IFN-gamma (Th1) and IL-4 (Th2), CD25/CD122 surface expression by flow cytometry Molecular immunology Medium 24321396

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Drusen complement components C3a and C5a promote choroidal neovascularization. Proceedings of the National Academy of Sciences of the United States of America 536 16452172
1982 Tumor-promoting phorbol esters stimulate C3b and C3b' receptor-mediated phagocytosis in cultured human monocytes. The Journal of experimental medicine 455 7153708
1975 Properdin: binding to C3b and stabilization of the C3b-dependent C3 convertase. The Journal of experimental medicine 411 1185108
2003 The proinflammatory mediators C3a and C5a are essential for liver regeneration. The Journal of experimental medicine 335 12975457
1980 Relation of putative thioester bond in C3 to activation of the alternative pathway and the binding of C3b to biological targets of complement. The Journal of experimental medicine 323 6903192
1979 Modulation of the classical pathway C3 convertase by plasma proteins C4 binding protein and C3b inactivator. Proceedings of the National Academy of Sciences of the United States of America 310 293746
2006 Structure of C3b reveals conformational changes that underlie complement activity. Nature 297 17051160
2000 A role for the C3a anaphylatoxin receptor in the effector phase of asthma. Nature 280 10984054
1983 Fibronectin and serum amyloid P component stimulate C3b- and C3bi-mediated phagocytosis in cultured human monocytes. The Journal of experimental medicine 259 6225825
1997 C3a and C5a stimulate chemotaxis of human mast cells. Blood 254 9108406
2011 Complement fragment C3a controls mutual cell attraction during collective cell migration. Developmental cell 250 22118769
2007 C5L2 is critical for the biological activities of the anaphylatoxins C5a and C3a. Nature 187 17322907
1983 Human platelet activation by C3a and C3a des-arg. The Journal of experimental medicine 184 6604123
2012 C3a and C5a promote renal ischemia-reperfusion injury. Journal of the American Society of Nephrology : JASN 183 22797180
2002 Complement c3a and c5a induce different signal transduction cascades in endothelial cells. Journal of immunology (Baltimore, Md. : 1950) 175 12165538
2003 Functional receptor for C3a anaphylatoxin is expressed by normal hematopoietic stem/progenitor cells, and C3a enhances their homing-related responses to SDF-1. Blood 174 12511407
2008 A new map of glycosaminoglycan and C3b binding sites on factor H. Journal of immunology (Baltimore, Md. : 1950) 170 18684951
1994 Complement peptides C3a- and C5a-induced mediator release from dissociated human skin mast cells. The Journal of investigative dermatology 168 7513741
1983 Generation of C3a anaphylatoxin from human C3 by human mast cell tryptase. Journal of immunology (Baltimore, Md. : 1950) 158 6339618
1996 A new biologic role for C3a and C3a desArg: regulation of TNF-alpha and IL-1 beta synthesis. Journal of immunology (Baltimore, Md. : 1950) 152 8617973
2002 Influence of C3 deficiency on atherosclerosis. Circulation 145 12081998
2004 C3a and C3b activation products of the third component of complement (C3) are critical for normal liver recovery after toxic injury. Journal of immunology (Baltimore, Md. : 1950) 136 15240660
1974 Receptor for soluble C3 and C3b on human lymphoblastoid (RAJI) cells. Properties and biologocal significance. The Journal of experimental medicine 132 4591176
2009 C3a mediates epithelial-to-mesenchymal transition in proteinuric nephropathy. Journal of the American Society of Nephrology : JASN 122 19158354
1999 Receptor for the C3a anaphylatoxin is expressed by neurons and glial cells. Glia 121 10340761
2012 A prevalent C3 mutation in aHUS patients causes a direct C3 convertase gain of function. Blood 119 22246034
1981 Membrane distribution and adsorptive endocytosis by C3b receptors on human polymorphonuclear leukocytes. The Journal of experimental medicine 119 7252422
2002 An anti-C3b(i) mAb enhances complement activation, C3b(i) deposition, and killing of CD20+ cells by rituximab. Blood 114 12393727
1985 Human C3b- and C4b-regulatory proteins: a new multi-gene family. Immunology today 110 25289982
2016 Complement peptide C3a stimulates neural plasticity after experimental brain ischaemia. Brain : a journal of neurology 109 27956400
1975 Purification and partial characterization of human and porcine C3a anaphylatoxin. The Journal of biological chemistry 102 803505
2013 Immune cell-derived C3a and C5a costimulate human T cell alloimmunity. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 99 24033923
2019 C3- and CR3-dependent microglial clearance protects photoreceptors in retinitis pigmentosa. The Journal of experimental medicine 96 31209071
2017 Complement C3a signaling facilitates skeletal muscle regeneration by regulating monocyte function and trafficking. Nature communications 96 29233958
2016 Characterization of a functional C3A liver spheroid model. Toxicology research 96 27746894
2017 Anti-Factor B and Anti-C3b Autoantibodies in C3 Glomerulopathy and Ig-Associated Membranoproliferative GN. Journal of the American Society of Nephrology : JASN 91 28096309
1979 Action of the C3b-inactivator on the cell-bound C3b. Journal of immunology (Baltimore, Md. : 1950) 86 448074
2014 Histopathology of MPGN and C3 glomerulopathies. Nature reviews. Nephrology 85 25447133
1999 Regulation of IL-6 synthesis in human peripheral blood mononuclear cells by C3a and C3a(desArg). Journal of immunology (Baltimore, Md. : 1950) 79 9886419
1987 The superfamily of C3b/C4b-binding proteins. Federation proceedings 78 2952524
2013 Eculizumab and recurrent C3 glomerulonephritis. Pediatric nephrology (Berlin, Germany) 76 23689905
2004 Variations in the C3, C3a receptor, and C5 genes affect susceptibility to bronchial asthma. Human genetics 76 15278436
2022 Complement C3a and C3a Receptor Activation Mediates Podocyte Injuries in the Mechanism of Primary Membranous Nephropathy. Journal of the American Society of Nephrology : JASN 75 35777783
1984 Increased expression of the C3b receptor by neutrophils and complement activation during haemodialysis. Clinical and experimental immunology 74 6232024
2011 Improvement of HepG2/C3a cell functions in a microfluidic biochip. Biotechnology and bioengineering 73 21337338
1985 Mouse monoclonal antibodies to the human C3b receptor. Molecular immunology 73 3160931
2005 The C3a receptor antagonist SB 290157 has agonist activity. Immunology letters 72 16154494
2013 Human complement C3 deficiency: Th1 induction requires T cell-derived complement C3a and CD46 activation. Molecular immunology 71 24321396
2009 Nociceptive sensitization by complement C5a and C3a in mouse. Pain 70 20031321
2008 C3a receptor antagonist attenuates brain injury after intracerebral hemorrhage. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 67 18728680
2020 C3a receptor blockade protects podocytes from injury in diabetic nephropathy. JCI insight 65 32161193
2016 Towards engineering carboxysomes into C3 plants. The Plant journal : for cell and molecular biology 64 26867858
1996 Extrahepatic secreted complement C3 contributes to circulating C3 levels in humans. Journal of immunology (Baltimore, Md. : 1950) 62 8609428
2012 Staphylococcus aureus proteins Sbi and Efb recruit human plasmin to degrade complement C3 and C3b. PloS one 60 23071827
2010 Complement fragments C3a and C5a: the salt and pepper of the immune response. European journal of immunology 60 20186746
1983 The human C3b receptor. Springer seminars in immunopathology 60 6227098
2010 Complement C3a, CpG oligos, and DNA/C3a complex stimulate IFN-α production in a receptor for advanced glycation end product-dependent manner. Journal of immunology (Baltimore, Md. : 1950) 59 20817881
2016 C3 Glomerulopathy. Pediatric nephrology (Berlin, Germany) 56 27056062
2013 C3a, C5a renal expression and their receptors are correlated to severity of IgA nephropathy. Journal of clinical immunology 56 24327134
1998 Both C3a and C3a(desArg) regulate interleukin-6 synthesis in human peripheral blood mononuclear cells. The Journal of infectious diseases 56 9607842
2020 The Complement C3a and C3a Receptor Pathway in Kidney Diseases. Frontiers in immunology 55 32973774
1983 C3 convertase of the alternative complement pathway. Demonstration of an active, stable C3b, Bb (Ni) complex. The Journal of biological chemistry 53 6553050
1998 Expression of a functional anaphylatoxin C3a receptor by astrocytes. Journal of neurochemistry 52 9832147
2006 Human plasmacytoid dendritic cells express receptors for anaphylatoxins C3a and C5a and are chemoattracted to C3a and C5a. The Journal of investigative dermatology 50 16778800
1991 Internalization pathway of C3b receptors in human neutrophils and its transmodulation by chemoattractant receptors stimulation. Cell regulation 49 1826092
1983 Enzymic assay of C3b receptor on intact cells and solubilized cells. The Biochemical journal 49 6222733
1978 Complement receptor subtypes C3b and C3d in lymphatic tissue and follicular lymphoma. British journal of cancer 46 646924
2022 Complement C3 and Activated Fragment C3a Are Involved in Complement Activation and Anti-Bacterial Immunity. Frontiers in immunology 45 35281048
2014 Activation of C3a receptor is required in cigarette smoke-mediated emphysema. Mucosal immunology 45 25465103
2012 Human C3a and C3a desArg anaphylatoxins have conserved structures, in contrast to C5a and C5a desArg. Protein science : a publication of the Protein Society 45 23184394
2009 Complement C3a regulates late asthmatic response and airway hyperresponsiveness in mice. Journal of immunology (Baltimore, Md. : 1950) 45 19684087
1986 Characterization of the human glomerular C3 receptor as the C3b/C4b complement type one (CR1) receptor. Journal of immunology (Baltimore, Md. : 1950) 45 2418113
2018 Treating C3 glomerulopathy with eculizumab. BMC nephrology 44 29329521
1999 C3a is made by proximal tubular HK-2 cells and activates them via the C3a receptor. Kidney international 43 10571781
1998 Anaphylatoxin C3a but not C3a(desArg) is a chemotaxin for the mouse macrophage cell line J774. European journal of immunology 42 9603462
2017 Characterization of C3 in C3 glomerulopathy. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 41 27507892
2011 Distinct roles for C3a and C5a in complement-induced tubulointerstitial injury. Kidney international 41 21677637
2006 Antifungal activity of C3a and C3a-derived peptides against Candida. Biochimica et biophysica acta 41 17169328
2018 C3a is required for ILC2 function in allergic airway inflammation. Mucosal immunology 40 30104625
2005 Anaphylatoxin C3a receptors in asthma. Respiratory research 40 15723703
2015 Complement Peptide C3a Promotes Astrocyte Survival in Response to Ischemic Stress. Molecular neurobiology 39 25972241
2006 Induction of C3 and CCL2 by C3a in keratinocytes: a novel autocrine amplification loop of inflammatory skin reactions. Journal of immunology (Baltimore, Md. : 1950) 38 16982879
2005 Complement C3a enhances CXCL12 (SDF-1)-mediated chemotaxis of bone marrow hematopoietic cells independently of C3a receptor. Journal of immunology (Baltimore, Md. : 1950) 37 16148115
1977 Receptor-binding sites on C3 and C3b. Journal of immunology (Baltimore, Md. : 1950) 37 864256
2016 Glycine decarboxylase in C3, C4 and C3-C4 intermediate species. Current opinion in plant biology 36 27038285
1980 Control of serum C3 levels by beta 1H and C3b inactivator. The Journal of laboratory and clinical medicine 36 6445926
2021 The Sez6 Family Inhibits Complement by Facilitating Factor I Cleavage of C3b and Accelerating the Decay of C3 Convertases. Frontiers in immunology 34 33936031
1999 C3a(desArg) does not bind to and signal through the human C3a receptor. Immunology letters 34 10232396
1996 Regulation of alternative pathway activation and C3a production by adipose cells. Obesity research 34 8946437
2021 Increased ratios of complement factors C3a to C3 in aqueous humor and serum mark glaucoma progression. Experimental eye research 33 33493474
2019 C3a and suPAR drive versican V1 expression in tubular cells of focal segmental glomerulosclerosis. JCI insight 32 30944246
2014 Vimentin mediates uptake of C3 exoenzyme. PloS one 32 24967582
2023 SARS-CoV-2 spike protein induces lung endothelial cell dysfunction and thrombo-inflammation depending on the C3a/C3a receptor signalling. Scientific reports 31 37452090
2019 Complement C3a promotes proliferation, migration and stemness in cutaneous squamous cell carcinoma. Journal of cellular and molecular medicine 31 30825266
2002 Albutensin A and complement C3a decrease food intake in mice. Peptides 31 11814627
2010 CNS-specific expression of C3a and C5a exacerbate demyelination severity in the cuprizone model. Molecular immunology 30 20813409
2022 The complement C3-complement factor D-C3a receptor signalling axis regulates cardiac remodelling in right ventricular failure. Nature communications 29 36109509
2019 Deficiency of C3a receptor attenuates the development of diabetic nephropathy. BMJ open diabetes research & care 29 31798904
1998 Cloning and characterization of rat C3a receptor: differential expression of rat C3a and C5a receptors by LPS stimulation. Biochemical and biophysical research communications 29 9464274
1988 C3 receptors on macrophages. Journal of cell science. Supplement 28 2978518

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