Introduction of C5AR1

The complement anaphylatoxin C5a is a strong chemoattractant and an effective inflammatory mediator, which, upon binding to its G protein-coupled membrane-bound receptor C5AR1 provokes and amplifies inflammatory reactions by inducing degranulation, cytokine release, and oxidative burst of immune cells. This receptor is the lynchpin of communication between complement activation and the cellular immune response. The genetic locus for C5AR1 consists of two exons separated by a large intron, a structure it shares with the other anaphylatoxin receptors. It is widely distributed within myeloid cells, and intracellular lymphocyte expression has also been reported. This receptor couples primarily to the Gα_i2 in cells such as neutrophils and mast cells.

Functions of C5AR1 Membrane Protein

C5AR1 has been reported to be involved in a wide range of diseases and here we present some of the examples. Firstly, the single nucleotide polymorphisms (SNPs) in C5AR1 are associated with chronic spontaneous urticaria (CSU) susceptibility and anti-histamine therapeutic efficacy, as well as the pathogenesis and prognosis of coronary artery disease. Secondly, C5a binding to C5aR1 plays an important role in promoting inflammatory response during the effector phase of allergic, infectious and autoimmune diseases. Moreover, the C5aR1 receptor is also expressed on neurons in the brain and C5aR1 antagonist, PMX205, decreases amyloid pathology and suppresses cognitive deficits in Alzheimer Disease (AD) mouse models. Additionally, C5aR1 participates in the pathogenesis of ascending urinary tract infection and in the cardiac dysfunction development during sepsis.

Fig.1 The interaction of C5a with C5aR. (Huberlang, 2003)

Applications of C5AR1 Membrane Protein in Literature

1. Dick J., et al. C5a receptor 1 promotes autoimmunity, neutrophil dysfunction and injury in experimental anti-myeloperoxidase glomerulonephritis. Kidney International. 2017, 93(3): 615-625. PMID: 29241626

This study investigated the role of C5aR1 in the generation of anti-myeloperoxidase autoimmunity and the effector responses resulting in renal injury using murine models.

2. Song N., et al. C5a receptor1 inhibition alleviates influenza virus-induced acute lung injury. International Immunopharmacology. 2018, 59: 12-20. PMID: 29621732

This study used C5aR1-deficient mice and mice treated with anti-C5aR1 antibody to study the C5a-C5aR1 axis during acute lung injury (ALI) induced influenza virus infection. The results showed that this axis played an important role in ALI and the inhibition of C5aR1 was a promising intervention and adjunctive treatment.

3. Naheed C., et al. The complement factor 5a receptor 1 has a pathogenic role in chronic inflammation and renal fibrosis in a murine model of chronic pyelonephritis. Kidney International. 2016, 90(3): 540-554. PMID: 27370410

This study investigated the role of C5aR1 in the development of chronic inflammation and renal fibrosis in a murine model of chronic pyelonephritis. The results showed that this receptor was involved in the bacterial colonization, upregulation of local inflammatory responses to uropathogenic E. coli, and impairment of the phagocytic function of phagocytes, which together resulted in the persistent bacterial colonization of the kidney, chronic renal inflammation, and subsequent tubulointerstitial fibrosis.

4. Benson M J., et al. A novel anticonvulsant mechanism via inhibition of complement receptor C5ar1 in murine epilepsy models. Neurobiology of Disease. 2015, 76: 87-97. PMID: 25681535

Due to the upregulation of C5aR1 in epilepsy models, this study investigated the therapeutic potential of C5aR1 as a target for anti-epileptic drugs using the PMX53, the C5aR1 antagonist.

5. Shi Y W., et al. Schisantherin A attenuates ischemia/reperfusion-induced neuronal injury in rats via regulation of TLR4 and C5aR1 signaling pathways. Brain Behavior & Immunity. 2017, 66: 244-256. PMID: 28690033

This study investigated the pathological changes and Toll-like receptor 4 (TLR4) and C5aR1 signaling pathways in vitro and in vivo models of ischemia and reperfusion (I/R), as well as the roles of schisantherin A on I/R brain injury and the mechanisms.

C5AR1 Preparation Options

Creative Biolabs is at the forefront of functional membrane protein solubilization, stabilization, and purification for applications such as antibody discovery and drug discovery. Our robust Magic™ Membrane Protein platform is developed and introduced to prepare different classes of membrane proteins, including GPCRs, ion channels, membrane transporters, etc. We can provide multiple choices to reconstitute your protein targets in their functional formats. You can always find a suitable format based on the protein chemistry and the downstream applications. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-C5AR1 antibody development services.

• Magic™ Membrane Protein Production Platform
• Magic™ Anti-Membrane Protein Antibody Discovery Platform

Creative Biolabs uses innovative technologies and customized chemistry that aims to adapt to the biochemical properties of the target during each step of development. Our expertise in the biochemistry of membrane proteins and reagents for isolation put us in a unique position to promote your excellent studies. Please feel free to contact us for more detailed information.

Reference

1. Huberlang, M. S, et al. (2003). Structure-function relationships of human c5a and c5ar. Journal of Immunology. 170(12), 6115-24.

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