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C5a1 receptor

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Target id: 32

Nomenclature: C5a1 receptor

Family: Complement peptide receptors

Contents:

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 350 19q13.32 C5AR1 complement C5a receptor 1 36
Mouse 7 351 7 8.77 cM C5ar1 complement component 5a receptor 1
Rat 7 352 1q21 C5ar1 complement C5a receptor 1
Previous and Unofficial Names Click here for help
CD88 | C5A | C5AR | C5R1 | complement C5a receptor | C5a anaphylatoxin chemotactic receptor | C5a-R | complement component 5a receptor 1 | C5aR1
Database Links Click here for help
Specialist databases
GPCRdb c5ar1_human (Hs), c5ar1_mouse (Mm), c5ar1_rat (Rn)
Other databases
Alphafold P21730 (Hs), P30993 (Mm), P97520 (Rn)
ChEMBL Target CHEMBL2373 (Hs), CHEMBL5746 (Mm), CHEMBL5770 (Rn)
Ensembl Gene ENSG00000197405 (Hs), ENSMUSG00000049130 (Mm), ENSRNOG00000047800 (Rn)
Entrez Gene 728 (Hs), 12273 (Mm), 113959 (Rn)
Human Protein Atlas ENSG00000197405 (Hs)
KEGG Gene hsa:728 (Hs), mmu:12273 (Mm), rno:113959 (Rn)
OMIM 113995 (Hs)
Pharos P21730 (Hs)
RefSeq Nucleotide NM_001736 (Hs), NM_007577 (Mm), NM_053619 (Rn)
RefSeq Protein NP_001727 (Hs), NP_031603 (Mm), NP_446071 (Rn)
UniProtKB P21730 (Hs), P30993 (Mm), P97520 (Rn)
Wikipedia C5AR1 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Structure of the complement C5a1 receptor (C5aR1) bound to the extra-helical antagonist NDT9513727.
PDB Id:  5O9H
Ligand:  NDT9513727
Resolution:  2.7Å
Species:  Human
References:  94
Natural/Endogenous Ligands Click here for help
C5a {Sp: Human}
C3a {Sp: Human}
C5a {Sp: Mouse}
C3a {Sp: Mouse}
C5a {Sp: Rat}
C3a {Sp: Rat}
C5a des-Arg {Sp: Human}
ribosomal protein S19 {Sp: Human}
Comments: C5a anaphylatoxin has a higher potency than C3a anaphylatoxin
Potency order of endogenous ligands (Human)
C5a (C5, P01031), C5a des-Arg (C5) > C3a (C3, P01024)  [2]

Download all structure-activity data for this target as a CSV file go icon to follow link

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[125I]C5a (human) Peptide Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Full agonist 8.7 pKd 52
⤷ pKd 8.7 (Kd 2x10-9 M) [52]
C5a {Sp: Human} Peptide Click here for species-specific activity table Immunopharmacology Ligand Hs Full agonist 8.0 – 9.0 pEC50 78,86
⤷ pEC50 8.0 – 9.0 (EC50 1x10-8 – 1x10-9 M) [78,86]
BM221 Peptide Hs Agonist 8.2 pEC50 38
⤷ pEC50 8.2 (EC50 5.8x10-9 M) [38]
BM213 Peptide Hs Agonist 7.2 pEC50 38
⤷ pEC50 7.2 (EC50 5.89x10-8 M) [38]
YSFKPMPLaR Peptide Click here for species-specific activity table Hs Agonist 5.5 pEC50 122
⤷ pEC50 5.5 (EC50 3.24x10-6 M) [122]
C5a {Sp: Human} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Immunopharmacology Ligand Hs Full agonist 9.1 – 9.2 pIC50 44,86
⤷ pIC50 9.1 – 9.2 [44,86]
NDT9513727 Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inverse agonist 7.9 pIC50 12
⤷ pIC50 7.9 (IC50 1.16x10-8 M) [12]
N-methyl-Phe-Lys-Pro-D-Cha-Cha-D-Arg-CO2H Peptide Hs Full agonist 7.6 pIC50 57,59
⤷ pIC50 7.6 [57,59]
C5a des-Arg {Sp: Human} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Partial agonist 6.2 – 6.4 pIC50 14
⤷ pIC50 6.2 – 6.4 [14]
YSFKPMPLaR Peptide Click here for species-specific activity table Hs Full agonist 5.4 – 6.7 pIC50 29
⤷ pIC50 5.4 – 6.7 (IC50 4.2x10-6 – 2x10-7 M) [29]
lactomedin 1 Peptide Hs Agonist - - 87,125
⤷ [87,125]
Eu-DTPA-[Ser27, Nle70]hC5a Peptide Click here for species-specific activity table Ligand is labelled Hs Agonist - - 39
⤷ [39]
Agonist Comments
YSFKPMPLaR is an agonist of both C5aR and C3aR. In addition to human cells it has been shown to have agonist actions in mice and rats [100,122]. RP S19 is an endogenous ribosomal protein, in the dimerised form it acts as an agonist of C5aR, however the referenced study [78] used recombinant protein. RP S19 gave a maximal reponse in a leukocyte chemotaxis assay at a concentration of 1nM [78]. Skp is a bacterial chaperone protein. IC50 values for agonists are derived from radioligand displacement assays.
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
CHIPS Peptide Hs Antagonist 9.0 pKd 89
⤷ pKd 9.0 [89]
W54011 Small molecule or natural product Hs Antagonist 8.7 pKi 103
⤷ pKi 8.7 [103]
NDT9520492 Small molecule or natural product Hs Antagonist 7.5 pKi 113
⤷ pKi 7.5 [113]
avacopan Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Antagonist 9.7 pIC50 9
⤷ pIC50 9.7 [9]
DF2593A Small molecule or natural product Hs Antagonist 8.3 pIC50 74
⤷ pIC50 8.3 [74]
ACT-1014-6470 Small molecule or natural product Immunopharmacology Ligand Hs Antagonist 8.0 pIC50 41
⤷ pIC50 8.0 (IC50 1.1x10-8 M) [41]
AcPhe-Orn-Pro-D-Cha-Trp-Arg Peptide Hs Antagonist 7.9 pIC50 116
⤷ pIC50 7.9 [116]
A8Δ71-73 Peptide Click here for species-specific activity table Mm Antagonist 7.6 pIC50 85
⤷ pIC50 7.6 (IC50 2.7x10-8 M) [85]
PMX205 Peptide Immunopharmacology Ligand Hs Antagonist 7.5 pIC50 67,70
⤷ pIC50 7.5 (IC50 3.1x10-8 M) [67,70]
PMX53 Peptide Hs Antagonist 7.1 – 7.7 pIC50 68,70,106,122
⤷ pIC50 7.1 – 7.7 (IC50 9x10-8 – 2.1x10-8 M) [68,70,106,122]
DF3016A Small molecule or natural product Hs Antagonist 7.3 pIC50 11
⤷ pIC50 7.3 (IC50 5x10-8 M) [11]
Description: Inhibition of C5a-induced human PMN migration
N-methyl-Phe-Lys-Pro-D-Cha-Trp-D-Arg-CO2H Peptide Hs Antagonist 7.2 pIC50 59
⤷ pIC50 7.2 [59]
JPE1375 Peptide Hs Antagonist 7.0 pIC50 95
⤷ pIC50 7.0 (IC50 1.11x10-7 M) [95]
C089 Peptide Hs Antagonist 6.7 pIC50 59
⤷ pIC50 6.7 (IC50 2.01x10-7 M) [59]
RPR121154 Small molecule or natural product Hs Antagonist 6.1 pIC50 6
⤷ pIC50 6.1 [6]
L-156,602 Peptide Hs Antagonist 5.7 pIC50 109
⤷ pIC50 5.7 [109]
View species-specific antagonist tables
Antagonist Comments
PMX53 is widely used as a parenterally- and orally-active antagonist of C5aR in mice and rats [90]. Although it has been demonstrated to block C5a binding in rat neutrophils (IC50 40nM), it does not inhibit C5a binding in murine cells [122]. However, it has specific C5aR antagonistic activity in vivo as demonstrated through comparisons with C5aR knockout mice [22]. PMX205 is also parenterally- and orally-active [90], but with greater lipophicity, and blood brain barrier penetrance than PMX53 [119-120]. PMX205 was also shown to be ineffective in C5aR knockout mice [55]. JPE1375 inhibits the chemotaxis of murine J774A.1 cells, but exhibits a reduced potency when compared to human neutrophils (IC50 420nM) [95]. A8 binds both C5aR and C5L2 with similar affinity, although the antagonistic properties of A8 at C5L2 remain untested [85]. In addition, other biologically relevant inhibitors of C5aR have been described. Chemotaxis inhibitory protein of S. aureus (CHIPS) is a 14.1 kDa antagonist of C5aR encoded on a bacteriophage. It has been demonstrated to have selective antagonistic properties against human C5aR in the micromolar concentration range [20].

CCX168 (avacopan) has been shown to be a high affinity small molecule antagonist of human C5a1 with an IC50 of 0.2nM [123].
Immunopharmacology Comments
C5aR is typically associated with the compement cascade and innate immunity.
MorphoSys have an anti-C5aR monoclonal antibody (MOR210; TJ210) in preclinical development as an immuno-oncology agent. The goal of anti-C5aR therapy is to reduce the effects that activation of the C5a/C5aR axis has on promoting cancer cell migration and invasiveness [47,69,80-81].
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Immune regulation
Immuno Process:  Chemotaxis & migration
Immuno Process:  Cellular signalling
Immuno Process:  Cytokine production & signalling
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family
G protein (identity unknown) 		Phospholipase C stimulation
Other - See Comments
Comments:  Studies of C5aR signalling have determined cell-specific activation of downstream pathways. For instance, in macrophages C5aR signals via protein kinase C (PKC) δ to induce NFκB activation and translocation to the nucleus, whereas in neutrophils C5aR induces activation of IκB, the NFκB inhibitor [40]. Additionally, activated C5aR has also been shown to associate with Wiskott-Aldrich Syndrome Protein (WASP), a regulator of Rho-GTPases and therefore, cytoskeletal turnover [107]. In mesenchymal stem cells C5a induces a chemotaxis that is pertussis toxin sensitive, indicating a Gi mediated response, and signalling via MAPK and Akt pathways [96]. C5aR has also been demonstrated to cause transactivation of the epidermal growth factor (EGF) receptor in human umbilical vein endothelial cells [97]. Heterodimer formation with C5a2 modulates signalling through C5a1, resulting in altered cytokine responses in human macrophages [16].
References:  101
Secondary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gq/G11 family Phospholipase C stimulation
References:  63
Tissue Distribution Click here for help
Mast cell subsets.
Species:  Human
Technique:  Immunocytochemistry.
References:  84
Cardiomyocytes
Species:  Human
Technique:  Northern blot
References:  42,115
Connective Tissue (synoviocytes, articular chondrocytes)
Species:  Human
Technique:  RT-PCR, immunocytochemistry
References:  83,126
Central Nervous System (astrocytes, microglia, neuron, neural stem cells, oligodendrocytes)
Species:  Human
Technique:  Immunohistochemistry
References:  35
Lung
Species:  Human
Technique:  Immunohistochemistry
References:  42
Liver
Species:  Human
Technique:  Northern blot
References:  42
Myeloid Leukocytes (neutrophil, eosinophil, basophil, monocytes)
Species:  Human
Technique:  Immunohistochemistry
References:  46,102
Vascular endothelial cells
Species:  Human
Technique:  Immunohistochemistry
References:  42
Vascular smooth muscle
Species:  Human
Technique:  Immunohistochemistry
References:  42,86
Eye (retinal pigment epithelial cells)
Species:  Human
Technique:  Flow cytometry
References:  33
Kidney
Species:  Human
Technique:  Immunohistochemistry
References:  35,77,82,91
Microvascular endothelial cells.
Species:  Mouse
Technique:  Radioligand binding.
References:  62
Central Nervous System (astrocytes, microglia, neuron, neural stem cells, oligodendrocytes)
Species:  Mouse
Technique:  Immunohistochemistry
References:  77,82,91
Central Nervous System (astrocytes, microglia, neuron, neural stem cells, oligodendrocytes)
Species:  Rat
Technique:  Immunohistochemistry
References:  77,82,91
Oligodendrocytes.
Species:  Rat
Technique:  RT-PCR.
References:  77
Tissue Distribution Comments
C5a1 was not found in pulmonary, hepatic, and intestinal epithelial cells, or lymphocytes in humans when examined with immunohistochemistry [26-27]. Although it has been previously reported that lymphocytes do not express C5aR, Lalli and colleagues (2008)[61] demonstrated a role for C5aR in T-cell survival. The techniques employed involved the use of a C5aR knockout mouse and a C5aR antagonist, to infer a function for C5aR on T-cells. No direct expression of either C5aR transcript or protein was demonstrated in this study. In addition, a recent study describing a GFP knock-in mouse, under the control of the C5aR promotor, failed to show GFP expression in either naïve or activated T-lymphocytes [24].
Expression Datasets Click here for help

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays Click here for help
Chemotaxis
Species:  Human
Tissue:  Granulocytes, monocytes, RBL-2H3 C5aR transfected cells
Response measured:  Migration of cells up concentration gradient
References:  18,23,86,96
Smooth muscle contraction
Species:  Human
Tissue:  Human umbilical artery
Response measured:  Contraction of smooth muscle
References:  15,86
ERK1/2 phosphorylation
Species:  Human
Tissue:  Mesenchymal stem cell, C5aR-transfected CHO cells, neutrophils
Response measured:  Increase in Phospho-ERK1/2 by Western blot
References:  92,96,105
Enzyme Release/Degranulation
Species:  Human
Tissue:  Neutrophils, RBL-2H3 C5aR transfected cells
Response measured:  Increase in myeloperoxidase, hydrogen peroxide (?peroxidase) and b-hexosaminidase release
References:  50,72,86
Intracellular calcium release
Species:  Human
Tissue:  Neutrophils, monocytes, HMC-1 cells, U937 cells, Rat hippocampal neurons
Response measured:  Transient increase in intracellular calcium concentrations upon receptor activation.
References:  79,82
Measurement of degranulation in rat basophilic leukemia cells transfected with the human C5a receptor.
Species:  Human
Tissue:  Rat basophilic leukemia cells.
Response measured:  Degranulation.
References:  45
Physiological Functions Click here for help
Chemotaxis.
Species:  Human
Tissue:  Granulocyte.
References:  73
Hepatocyte growth factor.
Species:  Rat
Tissue:  Liver.
References:  19
MAP kinase activation.
Species:  Mouse
Tissue:  Pituitary.
References:  32
Chemotaxis.
Species:  Human
Tissue:  Lymphocyte subsets.
References:  60
NF-κB activation.
Species:  Human
Tissue:  Neurons.
References:  82
Chemotaxis
Species:  Human
Tissue:  T cells, mesenchymal stem cells, dermal microvascular endothelial cells
References:  76,96
Apoptosis under oxygen/glucose deprivation
Species:  Mouse
Tissue:  Cortical neurons
References:  88
Chemokine (CCL2, CXCL2) release
Species:  Mouse
Tissue:  Microvascular endothelial cells
References:  62
Chemokine (IL-8) release
Species:  Human
Tissue:  Epithelial cells (lung, eye)
References:  33,42
Neutrophil extravasation
Species:  Mouse
Tissue:  Brain
References:  98
Neutropaenia
Species:  Rat
Tissue:  Blood
References:  99
Cell survival
Species:  Human
Tissue:  T-Lymphocytes
References:  61
Proliferation
Species:  Rat
Tissue:  Cerebellar granular neurons
References:  13
Histamine release
Species:  Human
Tissue:  Mast cells, basophils
References:  34
Degranulation
Species:  Human
Tissue:  Neutrophils, mast cells
References:  43,50,86
Physiological Consequences of Altering Gene Expression Click here for help
Mice with receptor knockout exhibit increased susceptibility and lethality to Pseudomonas aeruginosa infection.
Species:  Mouse
Tissue:  Lung
Technique:  Gene knockouts
References:  54
Adenovirus-mediated in vivo silencing of the C5a receptor.
Species:  Mouse
Tissue: 
Technique:  RNA interference
References:  104
Human C5a receptor knock-in mice facilitate the production and assessment of anti-inflammatory monoclonal antibodies.
Species:  Mouse
Tissue: 
Technique:  Transgenesis
References:  64
In rat models of induced sepsis using cecal ligation and puncture (CLP), those rats treated with antibodies against C5aR showed reduced levels of bacteraemia and improved survival rates.
Species:  Rat
Tissue:  Neutrophils
Technique:  Antibody targeting of the receptor
References:  17,49,51
C5aR blocking antibody-treated or C5aR-/- mice, increased survival and decreased serum proinflammatory cytokines in the caecal ligation and puncture model of sepsis. C5aR blocking antibody also reduces bacteraemia, as measure by bacterial colony forming units in blood, this is likely due to an impairment of neutrophil phagocytic activity in the presence of high C5a concentrations
Species:  Mouse
Tissue:  Neutrophils
Technique:  Antibody treatment and gene knockout
References:  93
In a dextran sulphate-induced colitis mouse model, C5AR1 knockout mice showed reduced severity of symptoms and lower expression of inflammatory mediators compared to wildtype controls. However, in chronic colitis, the pathology of C5aR-deficient mice worsens.
Species:  Mouse
Tissue:  Cecum and colon
Technique:  Gene knockouts
References:  56
In a rat model of TNBS induced colitis, treatment with the C5aR antagonist, PMX53, reduced pathology and mortality.
Species:  Rat
Tissue:  Cecum and colon
Technique:  Treatment with receptor antagonist
References:  117
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
C5ar1tm1Cge C5ar1tm1Cge/C5ar1tm1Cge
involves: 129S4/SvJae		 MGI:88232  MP:0001800 abnormal humoral immune response PMID: 8781237 
C5ar1tm1Cge C5ar1tm1Cge/C5ar1tm1Cge
involves: 129S4/SvJae		 MGI:88232  MP:0008719 impaired neutrophil recruitment PMID: 8779720 
C5ar1tm1Cge C5ar1tm1Cge/C5ar1tm1Cge
involves: 129S4/SvJae		 MGI:88232  MP:0009763 increased sensitivity to induced morbidity/mortality PMID: 8779720 
C5ar1tm1Raw C5ar1tm1Raw/C5ar1tm1Raw
B6.Cg-C5ar1		 MGI:88232  MP:0008481 increased spleen germinal center number PMID: 18455242 
C5ar1tm1Cge C5ar1tm1Cge/C5ar1tm1Cge
involves: 129S4/SvJae		 MGI:88232  MP:0002412 increased susceptibility to bacterial infection PMID: 8779720 
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Alzheimer disease
Synonyms: Alzheimer's disease [Disease Ontology: DOID:10652]
Disease Ontology: DOID:10652
OMIM: 104300
Comments:  C5aR colocalises to microglia in amyloid plaques in the Tg2576 and hAPP mouse models of Alzheimer's disease. Inhbition of C5aR, through oral administration of PMX205, in these models reduces pathology and results in improved behavioural responses.
References:  1,31
Disease:  Amyotrophic lateral sclerosis
Disease Ontology: DOID:332
Orphanet: ORPHA803
Comments:  In both the SODG93A and NFL-/- mouse models of ALS, C5aR is upregulated. The upregulation occurs in the presymptomatic stages of the NFL-/- model and the author observed this upregulation within motor neurons. However, in the SODG93A model, there is no early upregulation of C5aR within motor neurons, the upregulation occurs in the end stages of the model within motor neurons and astrocytes. The link between C5aR upregulation and ALS pathology has only been confirmed in the SODG93A model, where blockade of C5aR signalling with orally administered PMX205 increased survival and motor performance.
References:  28,53,118
Disease:  Antiphospholipid syndrome
Disease Ontology: DOID:2988
OMIM: 107320
Orphanet: ORPHA80
Role:  C5aR functions as the activating receptor for neutrophils in antiphospholipid syndrome, neutrophil activation leads to the oxidative damage and pregancy loss characteristic of aPLS. Mice deficient in C5, or pharmacological blockage of C5aR, exhibit increased foetal growth and decreased foetal loss in aPLS.
References:  37,114
Disease:  Huntington disease
Synonyms: Huntington's disease [Disease Ontology: DOID:12858]
Disease Ontology: DOID:12858
OMIM: 143100
Comments:  In a rat model of 3-nitropropionic acid-induced Huntington's disease, C5aR inhibition via oral administration of either PMX53 or PMX205 reduced the behavioural phenotype and striatal lesions histologically. A decrease in striatal astrocytosis was also demonstrated, however whether this was a cause or effect of the reduction in striatal lesions was not investigated.
References:  119
Disease:  Immunoglobulin A vasculitis
Synonyms: Henoch-Schönlein Purpura [Disease Ontology: DOID:11123]
Disease Ontology: DOID:11123
Orphanet: ORPHA761
Comments:  There is a possible association with immunoglobulin A vasculitis
References:  25
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Single nucleotide polymorphism Human c.450C>T 25
Disease:  Injury aggravation in neurotrauma
Role:  In a mouse model of neurotrauma, invoked by the application of a liquid nitrogen cooled probe to the skull, C5aR has been demonstrated to be a key factor in injury aggravation. The authors attribute the attenuation of injury in both mice treated with the C5aR antagonist, PMX53, and mice deficient in C5, to a reduced neutrophil infiltration of the brain tissue post-injury. By contrast, in a rat model of spinal cord contusion injury, C5aR inhibition with PMX53 worsended injury outcomes.
References:  8,98
Disease:  Ischemia-reperfusion injury
Role:  The role of C5aR has been well studied in ischaemia/reperfusion (IR) injury. C5aR has been demonstrated to play a proinflammatory role, contributing to pathology, in IR injury of the heart, kidney, liver, intestine, and brain.
References:  3-5,21,30,66,111,124,127
Disease:  Psoriasis
Description: A long-term autoimmune disease characterized by patches of red, itchy, and scaly skin. Five types of psoriasis are recognised: plaque (psoriasis vulgari), guttate, inverse, pustular, and erythrodermic, with plaque psoriasis being the most common type.
Disease Ontology: DOID:8893
Role:  Evidence of a role for C5aR in psoriasis stems from the observation that the ligands for C5aR, C5a/C5a-des-arg, are the most abundant cytokine isolated from human psoriatic scales.
References:  10,75
Disease:  Rheumatoid arthritis
Disease Ontology: DOID:7148
OMIM: 180300
Role:  In a rat model of antigen-induced monoarticular rheumatoid arthritis, oral administration of the C5aR antagonist PMX53 reduced oedema, inflammatory infiltrate and interarticular cytokines. However, in a double-blind, placebo controlled clinical trial, orally-administered PMX53 did not reduce synovial inflammation in rheumatoid arthritis patients.
References:  112,121
Clinically-Relevant Mutations and Pathophysiology Comments
The reported association of a C5aR polymorphism with Henoch-Schonlein purpura occurred in a population of patients with familial mediterranean fever. The C/T polymorphism is at base 450 in the coding sequence of C5aR. The association was noted, but the population size was insufficient to draw definitive conclusions [25]. Two other C5aR polymorphisms have been described but have no observable phenotype [7,108].
Gene Expression and Pathophysiology Click here for help
A reduction in the expression of C5AR1 on neutrophils, with increased levels in serum was seen in patients with progressive sepsis.
Tissue or cell type:  Neutrophils and serum
Pathophysiology:  Sepsis
Species:  Human
Technique:  Immunoblotting and flowcytometic analysis
References:  48,110
General Comments
Although C5aR is typically associated with the innate immune system, recently research on the receptor has elucidated novel roles. C5aR has been demonstrated on adult neural progenitor cells [91], mesenchymal stem cells [96] and perhaps has roles regulating the cell cycle in types of cancer [58,71].
Pharmacological inhibition of C5aR signalling ameliorates disease pathology in a mouse model of amyotrophic lateral sclerosis [65].

References

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1. Ager RR, Fonseca MI, Chu SH, Sanderson SD, Taylor SM, Woodruff TM, Tenner AJ. (2010) Microglial C5aR (CD88) expression correlates with amyloid-beta deposition in murine models of Alzheimer's disease. J Neurochem, 113 (2): 389-401. [PMID:20132482]

2. Ames RS, Nuthulaganti P, Kumar C. (1996) In Xenopus oocytes the human C3a and C5a receptors elicit a promiscuous response to the anaphylatoxins. FEBS Lett, 395 (2-3): 157-9. [PMID:8898085]

3. Arumugam TV, Shiels IA, Strachan AJ, Abbenante G, Fairlie DP, Taylor SM. (2003) A small molecule C5a receptor antagonist protects kidneys from ischemia/reperfusion injury in rats. Kidney Int, 63 (1): 134-42. [PMID:12472776]

4. Arumugam TV, Woodruff TM, Lathia JD, Selvaraj PK, Mattson MP, Taylor SM. (2009) Neuroprotection in stroke by complement inhibition and immunoglobulin therapy. Neuroscience, 158 (3): 1074-89. [PMID:18691639]

5. Arumugam TV, Woodruff TM, Stocks SZ, Proctor LM, Pollitt S, Shiels IA, Reid RC, Fairlie DP, Taylor SM. (2004) Protective effect of a human C5a receptor antagonist against hepatic ischaemia-reperfusion injury in rats. J Hepatol, 40 (6): 934-41. [PMID:15158333]

6. Astles PC, Brown TJ, Cox P, Halley F, LockeyPM, McCarthy C, McLayIM, Majid TN, Morley AD, Porter B et al.. (1997) New non-peptide C5a receptor antagonists. Bioorg Med Chem Lett, 7 (77): 907-912.

7. Barnes KC, Caraballo L, Muñoz M, Zambelli-Weiner A, Ehrlich E, Burki M, Jimenez S, Mathias RA, Stockton ML, Deindl P et al.. (2004) A novel promoter polymorphism in the gene encoding complement component 5 receptor 1 on chromosome 19q13.3 is not associated with asthma and atopy in three independent populations. Clin Exp Allergy, 34 (5): 736-44. [PMID:15144465]

8. Beck KD, Nguyen HX, Galvan MD, Salazar DL, Woodruff TM, Anderson AJ. (2010) Quantitative analysis of cellular inflammation after traumatic spinal cord injury: evidence for a multiphasic inflammatory response in the acute to chronic environment. Brain, 133 (Pt 2): 433-47. [PMID:20085927]

9. Bekker P, Dairaghi D, Seitz L, Leleti M, Wang Y, Ertl L, Baumgart T, Shugarts S, Lohr L, Dang T et al.. (2016) Characterization of Pharmacologic and Pharmacokinetic Properties of CCX168, a Potent and Selective Orally Administered Complement 5a Receptor Inhibitor, Based on Preclinical Evaluation and Randomized Phase 1 Clinical Study. PLoS ONE, 11 (10): e0164646. [PMID:27768695]

10. Bergh K, Iversen OJ, Lysvand H. (1993) Surprisingly high levels of anaphylatoxin C5a des Arg are extractable from psoriatic scales. Arch Dermatol Res, 285 (3): 131-4. [PMID:8503693]

11. Brandolini L, Grannonico M, Bianchini G, Colanardi A, Sebastiani P, Paladini A, Piroli A, Allegretti M, Varrassi G, Di Loreto S. (2019) Correction to: The Novel C5aR Antagonist DF3016A Protects Neurons Against Ischemic Neuroinflammatory Injury. Neurotox Res, 36 (2): 439. [PMID:31062231]

12. Brodbeck RM, Cortright DN, Kieltyka AP, Yu J, Baltazar CO, Buck ME, Meade R, Maynard GD, Thurkauf A, Chien DS et al.. (2008) Identification and characterization of NDT 9513727 [N,N-bis(1,3-benzodioxol-5-ylmethyl)-1-butyl-2,4-diphenyl-1H-imidazole-5-methanamine], a novel, orally bioavailable C5a receptor inverse agonist. J Pharmacol Exp Ther, 327 (3): 898-909. [PMID:18753409]

13. Bénard M, Raoult E, Vaudry D, Leprince J, Falluel-Morel A, Gonzalez BJ, Galas L, Vaudry H, Fontaine M. (2008) Role of complement anaphylatoxin receptors (C3aR, C5aR) in the development of the rat cerebellum. Mol Immunol, 45 (14): 3767-74. [PMID:18635264]

14. Cain SA, Monk PN. (2002) The orphan receptor C5L2 has high affinity binding sites for complement fragments C5a and C5a des-Arg(74). J Biol Chem, 277 (9): 7165-9. [PMID:11773063]

15. Cochrane CG, Müller-Eberhard HJ. (1968) The derivation of two distinct anaphylatoxin activities from the third and fifth components of human complement. J Exp Med, 127 (2): 371-86. [PMID:4383923]

16. Croker DE, Halai R, Fairlie DP, Cooper MA. (2013) C5a, but not C5a-des Arg, induces upregulation of heteromer formation between complement C5a receptors C5aR and C5L2. Immunol Cell Biol, 91 (10): 625-33. [PMID:24060963]

17. Czermak BJ, Sarma V, Pierson CL, Warner RL, Huber-Lang M, Bless NM, Schmal H, Friedl HP, Ward PA. (1999) Protective effects of C5a blockade in sepsis. Nat Med, 5 (7): 788-92. [PMID:10395324]

18. Daffern PJ, Pfeifer PH, Ember JA, Hugli TE. (1995) C3a is a chemotaxin for human eosinophils but not for neutrophils. I. C3a stimulation of neutrophils is secondary to eosinophil activation. J Exp Med, 181 (6): 2119-27. [PMID:7760001]

19. Daveau M, Benard M, Scotte M, Schouft MT, Hiron M, Francois A, Salier JP, Fontaine M. (2004) Expression of a functional C5a receptor in regenerating hepatocytes and its involvement in a proliferative signaling pathway in rat. J Immunol, 173 (5): 3418-24. [PMID:15322206]

20. de Haas CJ, Veldkamp KE, Peschel A, Weerkamp F, Van Wamel WJ, Heezius EC, Poppelier MJ, Van Kessel KP, van Strijp JA. (2004) Chemotaxis inhibitory protein of Staphylococcus aureus, a bacterial antiinflammatory agent. J Exp Med, 199 (5): 687-95. [PMID:14993252]

21. de Vries B, Köhl J, Leclercq WK, Wolfs TG, van Bijnen AA, Heeringa P, Buurman WA. (2003) Complement factor C5a mediates renal ischemia-reperfusion injury independent from neutrophils. J Immunol, 170 (7): 3883-9. [PMID:12646657]

22. Denny KJ, Coulthard LG, Jeanes A, Lisgo S, Simmons DG, Callaway LK, Wlodarczyk B, Finnell RH, Woodruff TM, Taylor SM. (2013) C5a receptor signaling prevents folate deficiency-induced neural tube defects in mice. J Immunol, 190 (7): 3493-9. [PMID:23420882]

23. Deuel TF, Senior RM, Huang JS, Griffin GL. (1982) Chemotaxis of monocytes and neutrophils to platelet-derived growth factor. J Clin Invest, 69 (4): 1046-9. [PMID:7076844]

24. Dunkelberger J, Zhou L, Miwa T, Song WC. (2012) C5aR expression in a novel GFP reporter gene knockin mouse: implications for the mechanism of action of C5aR signaling in T cell immunity. J Immunol, 188 (8): 4032-42. [PMID:22430734]

25. Erken E, Gunesacar R, Ozer HT. (2010) Investigation of C5a receptor gene 450 C/T polymorphism in Turkish patients with familial Mediterranean fever. Mol Biol Rep, 37 (1): 273-6. [PMID:19657723]

26. Fayyazi A, Sandau R, Duong LQ, Götze O, Radzun HJ, Schweyer S, Soruri A, Zwirner J. (1999) C5a receptor and interleukin-6 are expressed in tissue macrophages and stimulated keratinocytes but not in pulmonary and intestinal epithelial cells. Am J Pathol, 154 (2): 495-501. [PMID:10027407]

27. Fayyazi A, Scheel O, Werfel T, Schweyer S, Oppermann M, Götze O, Radzun HJ, Zwirner J. (2000) The C5a receptor is expressed in normal renal proximal tubular but not in normal pulmonary or hepatic epithelial cells. Immunology, 99 (1): 38-45. [PMID:10651939]

28. Ferraiuolo L, Heath PR, Holden H, Kasher P, Kirby J, Shaw PJ. (2007) Microarray analysis of the cellular pathways involved in the adaptation to and progression of motor neuron injury in the SOD1 G93A mouse model of familial ALS. J Neurosci, 27 (34): 9201-19. [PMID:17715356]

29. Finch AM, Vogen SM, Sherman SA, Kirnarsky L, Taylor SM, Sanderson SD. (1997) Biologically active conformer of the effector region of human C5a and modulatory effects of N-terminal receptor binding determinants on activity. J Med Chem, 40 (6): 877-84. [PMID:9083476]

30. Fleming SD, Mastellos D, Karpel-Massler G, Shea-Donohue T, Lambris JD, Tsokos GC. (2003) C5a causes limited, polymorphonuclear cell-independent, mesenteric ischemia/reperfusion-induced injury. Clin Immunol, 108 (3): 263-73. [PMID:14499250]

31. Fonseca MI, Ager RR, Chu SH, Yazan O, Sanderson SD, LaFerla FM, Taylor SM, Woodruff TM, Tenner AJ. (2009) Treatment with a C5aR antagonist decreases pathology and enhances behavioral performance in murine models of Alzheimer's disease. J Immunol, 183 (2): 1375-83. [PMID:19561098]

32. Francis K, Lewis BM, Monk PN, Ham J. (2008) Complement C5a receptors in the pituitary gland: expression and function. J Endocrinol, 199 (3): 417-24. [PMID:19020281]

33. Fukuoka Y, Medof EM. (2001) C5a receptor-mediated production of IL-8 by the human retinal pigment epithelial cell line, ARPE-19. Curr Eye Res, 23 (5): 320-5. [PMID:11910520]

34. Füreder W, Agis H, Willheim M, Bankl HC, Maier U, Kishi K, Müller MR, Czerwenka K, Radaszkiewicz T, Butterfield JH et al.. (1995) Differential expression of complement receptors on human basophils and mast cells. Evidence for mast cell heterogeneity and CD88/C5aR expression on skin mast cells. J Immunol, 155 (6): 3152-60. [PMID:7673728]

35. Gasque P, Singhrao SK, Neal JW, Götze O, Morgan BP. (1997) Expression of the receptor for complement C5a (CD88) is up-regulated on reactive astrocytes, microglia, and endothelial cells in the inflamed human central nervous system. Am J Pathol, 150 (1): 31-41. [PMID:9006319]

36. Gerard NP, Bao L, Xiao-Ping H, Eddy RL, Shows TB, Gerard C. (1993) Human chemotaxis receptor genes cluster at 19q13.3-13.4. Characterization of the human C5a receptor gene. Biochemistry, 32 (5): 1243-50. [PMID:8383526]

37. Girardi G, Berman J, Redecha P, Spruce L, Thurman JM, Kraus D, Hollmann TJ, Casali P, Caroll MC, Wetsel RA et al.. (2003) Complement C5a receptors and neutrophils mediate fetal injury in the antiphospholipid syndrome. J Clin Invest, 112 (11): 1644-54. [PMID:14660741]

38. Gorman DM, Li XX, Lee JD, Fung JN, Cui CS, Lee HS, Rolfe BE, Woodruff TM, Clark RJ. (2021) Development of Potent and Selective Agonists for Complement C5a Receptor 1 with In Vivo Activity. J Med Chem, 64 (22): 16598-16608. [PMID:34762432]

39. Gorman DM, Li XX, Payne CD, Cui CS, Lee JD, Rosengren KJ, Woodruff TM, Clark RJ. (2021) Development of Synthetic Human and Mouse C5a: Application to Binding and Functional Assays In Vitro and In Vivo. ACS Pharmacol Transl Sci, 4 (6): 1808-1817. [PMID:34927012]

40. Guo RF, Ward PA. (2005) Role of C5a in inflammatory responses. Annu Rev Immunol, 23: 821-52. [PMID:15771587]

41. Hammann-Hänni A, Kaufmann P, Klein G, Schmid K, Dingemanse J. (2023) Effect of Severe Renal Impairment on Pharmacokinetics, Safety, and Tolerability of ACT-1014-6470, a Novel Oral Complement Factor 5a Receptor 1 Antagonist. Clin Pharmacol Drug Dev, 12 (2): 152-158. [PMID:36285509]

42. Haviland DL, McCoy RL, Whitehead WT, Akama H, Molmenti EP, Brown A, Haviland JC, Parks WC, Perlmutter DH, Wetsel RA. (1995) Cellular expression of the C5a anaphylatoxin receptor (C5aR): demonstration of C5aR on nonmyeloid cells of the liver and lung. J Immunol, 154 (4): 1861-9. [PMID:7836770]

43. Heimbach L, Li Z, Berkowitz P, Zhao M, Li N, Rubenstein DS, Diaz LA, Liu Z. (2011) The C5a receptor on mast cells is critical for the autoimmune skin-blistering disease bullous pemphigoid. J Biol Chem, 286 (17): 15003-9. [PMID:21393236]

44. Higginbottom A, Cain SA, Woodruff TM, Proctor LM, Madala PK, Tyndall JD, Taylor SM, Fairlie DP, Monk PN. (2005) Comparative agonist/antagonist responses in mutant human C5a receptors define the ligand binding site. J Biol Chem, 280: 17831-17840. [PMID:15661745]

45. Higginbottom A, Wilkinson I, McCullough B, Lanza F, Azorsa DO, Partridge LJ, Monk PN. (2000) Antibody cross-linking of human CD9 and the high-affinity immunoglobulin E receptor stimulates secretion from transfected rat basophilic leukaemia cells. Immunology, 99 (4): 546-52. [PMID:10792502]

46. Hook WA, Siraganian RP, Wahl SM. (1975) Complement-induced histamine release from human basophils. I. Generation of activity in human serum. J Immunol, 114 (4): 1185-90. [PMID:46892]

47. Hu WH, Hu Z, Shen X, Dong LY, Zhou WZ, Yu XX. (2016) C5a receptor enhances hepatocellular carcinoma cell invasiveness via activating ERK1/2-mediated epithelial-mesenchymal transition. Exp Mol Pathol, 100 (1): 101-8. [PMID:26475622]

48. Huber-Lang M, Sarma JV, Rittirsch D, Schreiber H, Weiss M, Flierl M, Younkin E, Schneider M, Suger-Wiedeck H, Gebhard F et al.. (2005) Changes in the novel orphan, C5a receptor (C5L2), during experimental sepsis and sepsis in humans. J Immunol, 174 (2): 1104-10. [PMID:15634936]

49. Huber-Lang MS, Sarma JV, McGuire SR, Lu KT, Guo RF, Padgaonkar VA, Younkin EM, Laudes IJ, Riedemann NC, Younger JG et al.. (2001) Protective effects of anti-C5a peptide antibodies in experimental sepsis. FASEB J, 15 (3): 568-70. [PMID:11259369]

50. Huber-Lang MS, Sarma JV, McGuire SR, Lu KT, Padgaonkar VA, Younkin EM, Guo RF, Weber CH, Zuiderweg ER, Zetoune FS et al.. (2003) Structure-function relationships of human C5a and C5aR. J Immunol, 170 (12): 6115-24. [PMID:12794141]

51. Huber-Lang MS, Younkin EM, Sarma JV, McGuire SR, Lu KT, Guo RF, Padgaonkar VA, Curnutte JT, Erickson R, Ward PA. (2002) Complement-induced impairment of innate immunity during sepsis. J Immunol, 169 (6): 3223-31. [PMID:12218141]

52. Huey R, Hugli TE. (1985) Characterization of a C5a receptor on human polymorphonuclear leukocytes (PMN). J Immunol, 135 (3): 2063-8. [PMID:4020139]

53. Humayun S, Gohar M, Volkening K, Moisse K, Leystra-Lantz C, Mepham J, McLean J, Strong MJ. (2009) The complement factor C5a receptor is upregulated in NFL-/- mouse motor neurons. J Neuroimmunol, 210 (1-2): 52-62. [PMID:19286267]

54. Höpken UE, Lu B, Gerard NP, Gerard C. (1996) The C5a chemoattractant receptor mediates mucosal defence to infection. Nature, 383 (6595): 86-9. [PMID:8779720]

55. Jain U, Woodruff T, Stadnyk A. (2013) The C5a receptor antagonist PMX205 ameliorates experimentally induced colitis associated with increased IL-4 and IL-10. Br J Pharmacol, 168 (2): 488-501. [PMID:22924972]

56. Johswich K, Martin M, Bleich A, Kracht M, Dittrich-Breiholz O, Gessner JE, Suerbaum S, Wende E, Rheinheimer C, Klos A. (2009) Role of the C5a receptor (C5aR) in acute and chronic dextran sulfate-induced models of inflammatory bowel disease. Inflamm Bowel Dis, 15 (12): 1812-23. [PMID:19714742]

57. Kawai M, Quincy DA, Lane B, Mollison KW, Or YS, Luly JR, Carter GW. (1992) Structure-function studies in a series of carboxyl-terminal octapeptide analogues of anaphylatoxin C5a. J Med Chem, 35: 220-223. [PMID:1732540]

58. Kim DY, Martin CB, Lee SN, Martin BK. (2005) Expression of complement protein C5a in a murine mammary cancer model: tumor regression by interference with the cell cycle. Cancer Immunol Immunother, 54 (10): 1026-37. [PMID:15868168]

59. Konteatis ZD, Siciliano SJ, Van Riper G, Molineaux CJ, Pandya S, Fischer P, Rosen H, Mumford RA, Springer MS. (1994) Development of C5a receptor antagonists. Differential loss of functional responses. J Immunol, 153 (9): 4200-5. [PMID:7930622]

60. Kupp LI, Kosco MH, Schenkein HA, Tew JG. (1991) Chemotaxis of germinal center B cells in response to C5a. Eur J Immunol, 21 (11): 2697-701. [PMID:1936118]

61. Lalli PN, Strainic MG, Yang M, Lin F, Medof ME, Heeger PS. (2008) Locally produced C5a binds to T cell-expressed C5aR to enhance effector T-cell expansion by limiting antigen-induced apoptosis. Blood, 112 (5): 1759-66. [PMID:18567839]

62. Laudes IJ, Chu JC, Huber-Lang M, Guo RF, Riedemann NC, Sarma JV, Mahdi F, Murphy HS, Speyer C, Lu KT et al.. (2002) Expression and function of C5a receptor in mouse microvascular endothelial cells. J Immunol, 169 (10): 5962-70. [PMID:12421982]

63. Lee CH, Katz A, Simon MI. (1995) Multiple regions of G alpha 16 contribute to the specificity of activation by the C5a receptor. Mol Pharmacol, 47: 218-223. [PMID:7870028]

64. Lee H, Zahra D, Vogelzang A, Newton R, Thatcher J, Quan A, So T, Zwirner J, Koentgen F, Padkjaer SB et al.. (2006) Human C5aR knock-in mice facilitate the production and assessment of anti-inflammatory monoclonal antibodies. Nat Biotechnol, 24 (10): 1279-84. [PMID:16980974]

65. Lee JD, Kumar V, Fung JNT, Ruitenberg MJ, Noakes PG, Woodruff TM. (2017) Pharmacological inhibition of complement C5a-C5a 1 receptor signalling ameliorates disease pathology in the hSOD1 G93A mouse model of amyotrophic lateral sclerosis. Br J Pharmacol, 174 (8): 689-699. [PMID:28128456]

66. Lewis AG, Köhl G, Ma Q, Devarajan P, Köhl J. (2008) Pharmacological targeting of C5a receptors during organ preservation improves kidney graft survival. Clin Exp Immunol, 153 (1): 117-26. [PMID:18505432]

67. Li XX, Lee JD, Massey NL, Guan C, Robertson AAB, Clark RJ, Woodruff TM. (2020) Pharmacological characterisation of small molecule C5aR1 inhibitors in human cells reveals biased activities for signalling and function. Biochem Pharmacol, 180: 114156. [PMID:32682759]

68. Lillegard KE, Loeks-Johnson AC, Opacich JW, Peterson JM, Bauer AJ, Elmquist BJ, Regal RR, Gilbert JS, Regal JF. (2014) Differential effects of complement activation products c3a and c5a on cardiovascular function in hypertensive pregnant rats. J Pharmacol Exp Ther, 351 (2): 344-51. [PMID:25150279]

69. Maeda Y, Kawano Y, Wada Y, Yatsuda J, Motoshima T, Murakami Y, Kikuchi K, Imamura T, Eto M. (2015) C5aR is frequently expressed in metastatic renal cell carcinoma and plays a crucial role in cell invasion via the ERK and PI3 kinase pathways. Oncol Rep, 33 (4): 1844-50. [PMID:25682807]

70. March DR, Proctor LM, Stoermer MJ, Sbaglia R, Abbenante G, Reid RC, Woodruff TM, Wadi K, Paczkowski N, Tyndall JD et al.. (2004) Potent cyclic antagonists of the complement C5a receptor on human polymorphonuclear leukocytes. Relationships between structures and activity. Mol Pharmacol, 65 (4): 868-79. [PMID:15044616]

71. Martin BK. (2007) Transcriptional control of complement receptor gene expression. Immunol Res, 39 (1-3): 146-59. [PMID:17917062]

72. Monk PN, Pease JE, Barker MD. (1994) C5a stimulus-secretion coupling in rat basophilic leukaemia (RBL-2H3) cells transfected with the human C5a receptor is mediated by pertussis and cholera toxin-sensitive G proteins. Biochem Mol Biol Int, 32 (1): 13-20. [PMID:8012277]

73. Monk PN, Scola AM, Madala P, Fairlie DP. (2007) Function, structure and therapeutic potential of complement C5a receptors. Br J Pharmacol, 152 (4): 429-48. [PMID:17603557]

74. Moriconi A, Cunha TM, Souza GR, Lopes AH, Cunha FQ, Carneiro VL, Pinto LG, Brandolini L, Aramini A, Bizzarri C et al.. (2014) Targeting the minor pocket of C5aR for the rational design of an oral allosteric inhibitor for inflammatory and neuropathic pain relief. Proc Natl Acad Sci USA, 111 (47): 16937-42. [PMID:25385614]

75. Mrowietz U, Koch WA, Zhu K, Wiedow O, Bartels J, Christophers E, Schröder JM. (2001) Psoriasis scales contain C5a as the predominant chemotaxin for monocyte-derived dendritic cells. Exp Dermatol, 10 (4): 238-45. [PMID:11493312]

76. Nataf S, Davoust N, Ames RS, Barnum SR. (1999) Human T cells express the C5a receptor and are chemoattracted to C5a. J Immunol, 162 (7): 4018-23. [PMID:10201923]

77. Nataf S, Levison SW, Barnum SR. (2001) Expression of the anaphylatoxin C5a receptor in the oligodendrocyte lineage. Brain Res, 894 (2): 321-6. [PMID:11251209]

78. Nishiura H, Shibuya Y, Yamamoto T. (1998) S19 ribosomal protein cross-linked dimer causes monocyte-predominant infiltration by means of molecular mimicry to complement C5a. Lab Invest, 78 (12): 1615-23. [PMID:9881961]

79. Nishiura H, Zhao R, Yamamoto T. (2011) The role of the ribosomal protein S19 C-terminus in altering the chemotaxis of leucocytes by causing functional differences in the C5a receptor response. J Biochem, 150 (3): 271-7. [PMID:21613290]

80. Nitta H, Murakami Y, Wada Y, Eto M, Baba H, Imamura T. (2014) Cancer cells release anaphylatoxin C5a from C5 by serine protease to enhance invasiveness. Oncol Rep, 32 (4): 1715-9. [PMID:25050844]

81. Nitta H, Wada Y, Kawano Y, Murakami Y, Irie A, Taniguchi K, Kikuchi K, Yamada G, Suzuki K, Honda J et al.. (2013) Enhancement of human cancer cell motility and invasiveness by anaphylatoxin C5a via aberrantly expressed C5a receptor (CD88). Clin Cancer Res, 19 (8): 2004-13. [PMID:23287562]

82. O'Barr SA, Caguioa J, Gruol D, Perkins G, Ember JA, Hugli T, Cooper NR. (2001) Neuronal expression of a functional receptor for the C5a complement activation fragment. J Immunol, 166 (6): 4154-62. [PMID:11238666]

83. Onuma H, Masuko-Hongo K, Yuan G, Sakata M, Nakamura H, Kato T, Aoki H, Nishioka K. (2002) Expression of the anaphylatoxin receptor C5aR (CD88) by human articular chondrocytes. Rheumatol Int, 22 (2): 52-5. [PMID:12070675]

84. Oskeritzian CA, Zhao W, Min HK, Xia HZ, Pozez A, Kiev J, Schwartz LB. (2005) Surface CD88 functionally distinguishes the MCTC from the MCT type of human lung mast cell. J Allergy Clin Immunol, 115 (6): 1162-8. [PMID:15940129]

85. Otto M, Hawlisch H, Monk PN, Müller M, Klos A, Karp CL, Köhl J. (2004) C5a mutants are potent antagonists of the C5a receptor (CD88) and of C5L2: position 69 is the locus that determines agonism or antagonism. J Biol Chem, 279 (1): 142-51. [PMID:14570896]

86. Paczkowski NJ, Finch AM, Whitmore JB, Short AJ, Wong AK, Monk PN, Cain SA, Fairlie DP, Taylor SM. (1999) Pharmacological characterization of antagonists of the C5a receptor. Br J Pharmacol, 128 (7): 1461-6. [PMID:10602324]

87. Pandey S, Li XX, Srivastava A, Baidya M, Kumari P, Dwivedi H, Chaturvedi M, Ghosh E, Woodruff TM, Shukla AK. (2019) Partial ligand-receptor engagement yields functional bias at the human complement receptor, C5aR1. J Biol Chem, 294 (24): 9416-9429. [PMID:31036565]

88. Pavlovski D, Thundyil J, Monk PN, Wetsel RA, Taylor SM, Woodruff TM. (2012) Generation of complement component C5a by ischemic neurons promotes neuronal apoptosis. FASEB J, 26 (9): 3680-90. [PMID:22651932]

89. Postma B, Poppelier MJ, van Galen JC, Prossnitz ER, van Strijp JA, de Haas CJ, van Kessel KP. (2004) Chemotaxis inhibitory protein of Staphylococcus aureus binds specifically to the C5a and formylated peptide receptor. J Immunol, 172 (11): 6994-7001. [PMID:15153520]

90. Proctor LM, Woodruff TM, Sharma P, Shiels IA, Taylor SM. (2006) Transdermal pharmacology of small molecule cyclic C5a antagonists. Adv Exp Med Biol, 586: 329-45. [PMID:16893082]

91. Rahpeymai Y, Hietala MA, Wilhelmsson U, Fotheringham A, Davies I, Nilsson AK, Zwirner J, Wetsel RA, Gerard C, Pekny M et al.. (2006) Complement: a novel factor in basal and ischemia-induced neurogenesis. EMBO J, 25 (6): 1364-74. [PMID:16498410]

92. Riedemann NC, Guo RF, Hollmann TJ, Gao H, Neff TA, Reuben JS, Speyer CL, Sarma JV, Wetsel RA, Zetoune FS et al.. (2004) Regulatory role of C5a in LPS-induced IL-6 production by neutrophils during sepsis. FASEB J, 18 (2): 370-2. [PMID:14688199]

93. Rittirsch D, Flierl MA, Nadeau BA, Day DE, Huber-Lang M, Mackay CR, Zetoune FS, Gerard NP, Cianflone K, Köhl J et al.. (2008) Functional roles for C5a receptors in sepsis. Nat Med, 14 (5): 551-7. [PMID:18454156]

94. Robertson N, Rappas M, Doré AS, Brown J, Bottegoni G, Koglin M, Cansfield J, Jazayeri A, Cooke RM, Marshall FH. (2018) Structure of the complement C5a receptor bound to the extra-helical antagonist NDT9513727. Nature, 553 (7686): 111-114. [PMID:29300009]

95. Schnatbaum K, Locardi E, Scharn D, Richter U, Hawlisch H, Knolle J, Polakowski T. (2006) Peptidomimetic C5a receptor antagonists with hydrophobic substitutions at the C-terminus: increased receptor specificity and in vivo activity. Bioorg Med Chem Lett, 16 (19): 5088-92. [PMID:16876401]

96. Schraufstatter IU, Discipio RG, Zhao M, Khaldoyanidi SK. (2009) C3a and C5a are chemotactic factors for human mesenchymal stem cells, which cause prolonged ERK1/2 phosphorylation. J Immunol, 182 (6): 3827-36. [PMID:19265162]

97. Schraufstatter IU, Trieu K, Sikora L, Sriramarao P, DiScipio R. (2002) Complement c3a and c5a induce different signal transduction cascades in endothelial cells. J Immunol, 169 (4): 2102-10. [PMID:12165538]

98. Sewell DL, Nacewicz B, Liu F, Macvilay S, Erdei A, Lambris JD, Sandor M, Fabry Z. (2004) Complement C3 and C5 play critical roles in traumatic brain cryoinjury: blocking effects on neutrophil extravasation by C5a receptor antagonist. J Neuroimmunol, 155 (1-2): 55-63. [PMID:15342196]

99. Short A, Wong AK, Finch AM, Haaima G, Shiels IA, Fairlie DP, Taylor SM. (1999) Effects of a new C5a receptor antagonist on C5a- and endotoxin-induced neutropenia in the rat. Br J Pharmacol, 126 (3): 551-4. [PMID:10188960]

100. Short AJ, Paczkowski NJ, Vogen SM, Sanderson SD, Taylor SM. (1999) Response-selective C5a agonists: differential effects on neutropenia and hypotension in the rat. Br J Pharmacol, 128 (3): 511-4. [PMID:10516626]

101. Siciliano SJ, Rollins TE, Springer MS. (1990) Interaction between the C5a receptor and Gi in both the membrane-bound and detergent-solubilized states. J Biol Chem, 265 (32): 19568-74. [PMID:2123189]

102. Soruri A, Kim S, Kiafard Z, Zwirner J. (2003) Characterization of C5aR expression on murine myeloid and lymphoid cells by the use of a novel monoclonal antibody. Immunol Lett, 88 (1): 47-52. [PMID:12853161]

103. Sumichika H, Sakata K, Sato N, Takeshita S, Ishibuchi S, Nakamura M, Kamahori T, Ehara S, Itoh K, Ohtsuka T et al.. (2002) Identification of a potent and orally active non-peptide C5a receptor antagonist. J Biol Chem, 277 (51): 49403-7. [PMID:12384495]

104. Sun L, Gao H, Sarma VJ, Guo RF, Ward PA. (2006) Adenovirus-mediated in vivo silencing of anaphylatoxin receptor C5aR. J Biomed Biotechnol, 2006 (4): 28945. [PMID:17057363]

105. Suvorova ES, Gripentrog JM, Oppermann M, Miettinen HM. (2008) Role of the carboxyl terminal di-leucine in phosphorylation and internalization of C5a receptor. Biochim Biophys Acta, 1783 (6): 1261-70. [PMID:18346468]

106. Tamamis P, Kieslich CA, Nikiforovich GV, Woodruff TM, Morikis D, Archontis G. (2014) Insights into the mechanism of C5aR inhibition by PMX53 via implicit solvent molecular dynamics simulations and docking. BMC Biophys, 7: 5. [PMID:25170421]

107. Tardif M, Brouchon L, Rabiet MJ, Boulay F. (2003) Direct binding of a fragment of the Wiskott-Aldrich syndrome protein to the C-terminal end of the anaphylatoxin C5a receptor. Biochem J, 372 (Pt 2): 453-63. [PMID:12600272]

108. Ten RM, Carmona EM, Babovic-Vuksanovic D, Katzmann JA. (1999) Mannose-binding lectin deficiency associated with neutrophil chemotactic unresponsiveness to C5a. J Allergy Clin Immunol, 104 (2 Pt 1): 419-24. [PMID:10452765]

109. Tsuji RF, Yamakoshi J, Uramoto M, Koshino H, Saito M, Kikuchi M, Masuda T. (1995) Anti-inflammatory effects and specificity of L-156,602: comparison of effects on concanavalin A and zymosan-induced footpad edema, and contact sensitivity response. Immunopharmacology, 29 (1): 79-87. [PMID:7768675]

110. Unnewehr H, Rittirsch D, Sarma JV, Zetoune F, Flierl MA, Perl M, Denk S, Weiss M, Schneider ME, Monk PN et al.. (2013) Changes and regulation of the C5a receptor on neutrophils during septic shock in humans. J Immunol, 190 (8): 4215-25. [PMID:23479227]

111. Van Beek J, Bernaudin M, Petit E, Gasque P, Nouvelot A, MacKenzie ET, Fontaine M. (2000) Expression of receptors for complement anaphylatoxins C3a and C5a following permanent focal cerebral ischemia in the mouse. Exp Neurol, 161 (1): 373-82. [PMID:10683302]

112. Vergunst CE, Gerlag DM, Dinant H, Schulz L, Vinkenoog M, Smeets TJ, Sanders ME, Reedquist KA, Tak PP. (2007) Blocking the receptor for C5a in patients with rheumatoid arthritis does not reduce synovial inflammation. Rheumatology (Oxford), 46 (12): 1773-8. [PMID:17965442]

113. Waters SM, Brodbeck RM, Steflik J, Yu J, Baltazar C, Peck AE, Severance D, Zhang LY, Currie K, Chenard BL et al.. (2005) Molecular characterization of the gerbil C5a receptor and identification of a transmembrane domain V amino acid that is crucial for small molecule antagonist interaction. J Biol Chem, 280 (49): 40617-23. [PMID:16230349]

114. Weiler H. (2008) Tracing the molecular pathogenesis of antiphospholipid syndrome. J Clin Invest, 118 (10): 3276-8. [PMID:18802489]

115. Wetsel RA. (1995) Expression of the complement C5a anaphylatoxin receptor (C5aR) on non-myeloid cells. Immunol Lett, 44 (2-3): 183-7. [PMID:7797249]

116. Wong AK, Finch AM, Pierens GK, Craik DJ, Taylor SM, Fairlie DP. (1998) Small molecular probes for G-protein-coupled C5a receptors: conformationally constrained antagonists derived from the C terminus of the human plasma protein C5a. J Med Chem, 41 (18): 3417-25. [PMID:9719594]

117. Woodruff TM, Arumugam TV, Shiels IA, Reid RC, Fairlie DP, Taylor SM. (2003) A potent human C5a receptor antagonist protects against disease pathology in a rat model of inflammatory bowel disease. J Immunol, 171 (10): 5514-20. [PMID:14607958]

118. Woodruff TM, Costantini KJ, Crane JW, Atkin JD, Monk PN, Taylor SM, Noakes PG. (2008) The complement factor C5a contributes to pathology in a rat model of amyotrophic lateral sclerosis. J Immunol, 181 (12): 8727-34. [PMID:19050293]

119. Woodruff TM, Crane JW, Proctor LM, Buller KM, Shek AB, de Vos K, Pollitt S, Williams HM, Shiels IA, Monk PN et al.. (2006) Therapeutic activity of C5a receptor antagonists in a rat model of neurodegeneration. FASEB J, 20 (9): 1407-17. [PMID:16816116]

120. Woodruff TM, Pollitt S, Proctor LM, Stocks SZ, Manthey HD, Williams HM, Mahadevan IB, Shiels IA, Taylor SM. (2005) Increased potency of a novel complement factor 5a receptor antagonist in a rat model of inflammatory bowel disease. J Pharmacol Exp Ther, 314 (2): 811-7. [PMID:15879003]

121. Woodruff TM, Strachan AJ, Dryburgh N, Shiels IA, Reid RC, Fairlie DP, Taylor SM. (2002) Antiarthritic activity of an orally active C5a receptor antagonist against antigen-induced monarticular arthritis in the rat. Arthritis Rheum, 46 (9): 2476-85. [PMID:12355496]

122. Woodruff TM, Strachan AJ, Sanderson SD, Monk PN, Wong AK, Fairlie DP, Taylor SM. (2001) Species dependence for binding of small molecule agonist and antagonists to the C5a receptor on polymorphonuclear leukocytes. Inflammation, 25 (3): 171-7. [PMID:11403208]

123. Xiao H, Dairaghi DJ, Powers JP, Ertl LS, Baumgart T, Wang Y, Seitz LC, Penfold ME, Gan L, Hu P et al.. (2014) C5a receptor (CD88) blockade protects against MPO-ANCA GN. J Am Soc Nephrol, 25 (2): 225-31. [PMID:24179165]

124. Xu DZ, Zaets SB, Chen R, Lu Q, Rajan H, Yang X, Zhang J, Feketova E, Bogdan N, Deitch EA et al.. (2009) Elimination of C5aR prevents intestinal mucosal damage and attenuates neutrophil infiltration in local and remote organs. Shock, 31 (5): 493-9. [PMID:18791492]

125. Yoshikawa M. (2015) Bioactive peptides derived from natural proteins with respect to diversity of their receptors and physiological effects. Peptides, 72: 208-25. [PMID:26297549]

126. Yuan G, Wei J, Zhou J, Hu H, Tang Z, Zhang G. (2003) Expression of C5aR (CD88) of synoviocytes isolated from patients with rheumatoid arthritis and osteoarthritis. Chin Med J, 116 (9): 1408-12. [PMID:14527377]

127. Zhang H, Qin G, Liang G, Li J, Barrington RA, Liu DX. (2007) C5aR-mediated myocardial ischemia/reperfusion injury. Biochem Biophys Res Commun, 357 (2): 446-52. [PMID:17416341]

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