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Gene Review

C5ar1  -  complement component 5a receptor 1

Mus musculus

Synonyms: C5a anaphylatoxin chemotactic receptor, C5a anaphylatoxin chemotactic receptor 1, C5a-R, C5aR, C5ar, ...
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Disease relevance of C5ar1


Psychiatry related information on C5ar1


High impact information on C5ar1

  • Small molecule inhibitors of the C5a receptor had antifibrotic effects in vivo, and common haplotype-tagging polymorphisms of the human gene C5 were associated with advanced fibrosis in chronic hepatitis C virus infection [5].
  • Here we show that mice deficient in the chemoattractant C5a receptor, in comparison to their wild-type littermates, were unable to clear intrapulmonary-instilled Pseudomonas aeruginosa, despite a marked increase in neutrophil influx, and succumbed to pneumonia [2].
  • C5aR- deficient mice exhibit decreased migration of neutrophils and decreased levels of TNF-alpha and interleukin 6 in the peritoneal reverse passive Arthus reaction compared to their wild-type littermates [3].
  • Impaired inflammatory responses in the reverse arthus reaction through genetic deletion of the C5a receptor [3].
  • In this study, we compare the effect of C5aR deficiency in immune complex-induced inflammation in the peritoneal cavity and skin with the results derived from our immune complex alveolitis model [3].

Chemical compound and disease context of C5ar1

  • Ca(2+) signaling was abolished only in mutant cells pretreated with pertussis toxin, suggesting that the C5a receptor couples to both Galpha15 and Galphai in vivo [6].
  • We induced the passive reverse Arthus reaction to IgG immune complexes (IC) at different tissue sites in mice lacking C3 treated or not with a C5aR-specific antagonist, or in mice lacking mast cells (Kit(W)/Kit(W-v) mice), and compared the inflammatory responses with those in the corresponding wild-type mice [7].
  • In both strains of genetically altered mice, the severity of pancreatitis and pancreatitis-associated lung injury was greater than that noted in the comparison wild-type strains of C5aR- and C5-sufficient animals [8].

Biological context of C5ar1

  • Upon administration of anti-erythrocyte antibodies, upregulation of activating Fcgamma receptors (FcgammaRs) on Kupffer cells, as observed in WT mice, was absent in C5aR-deficient mice, and FcgammaR-mediated in vivo erythrophagocytosis was impaired [9].
  • Importantly, C5aR-deficient mice exhibited a similar, increased allergic phenotype [10].
  • In contrast, up until now, no specific contribution of C5a and its receptor, C5aR, was recognized in diseases of antibody-dependent type II autoimmunity [9].
  • Here we report that local pharmacological targeting of the C5a receptor (C5aR) prior to initial allergen sensitization in murine models of inhalation tolerance or allergic asthma resulted in either induction or marked enhancement of Th2-polarized immune responses, airway inflammation, and AHR [10].
  • Furthermore, blocking of the C5aR pathway had no influence on renal apoptosis [11].

Anatomical context of C5ar1

  • Pulmonary allergen exposure in C5aR-targeted mice resulted in increased sensitization and accumulation of CD4+ CD69+ T cells associated with a marked increase in pulmonary myeloid, but not plasmacytoid, DC numbers [10].
  • We show that ablation of C5a receptor signaling abrogates neutrophil recruitment in wild-type mice and prevents the enhancement of neutrophil migration seen in FcgammaRIIB(-/-) mice, suggesting that C5aR signaling is the crucial initial event upstream of FcgammaR signaling [12].
  • Of note, C5aR but not C3aR inhibition reduced lymphocyte numbers in bronchoalveolar lavage fluid [13].
  • On the other hand, C5aR deficient mice are either protected from tissue injury induced by ICs, as in the lung, or the degree of the inflammatory response is markedly attenuated, as in peritoneum and skin [14].
  • Expression and function of C5a receptor in mouse microvascular endothelial cells [15].

Associations of C5ar1 with chemical compounds

  • In addition, AHR was absent in complement C5 and C5a receptor-deficient mice [16].
  • A series of studies has been performed in mice with engineered deficiencies of either FcgammaRs, the complement components C3, C4 or the C5a receptor [14].
  • Distinct tissue site-specific requirements of mast cells and complement components C3/C5a receptor in IgG immune complex-induced injury of skin and lung [7].
  • Generation of an expressible cDNA for the mouse C5a receptor was accomplished using the polymerase chain reaction and a sense oligodeoxynucleotide primer which included an initiation codon just 5' to the sequence encoding the N-linked glycosylation site [17].
  • C3a and C5a mediate these effects by binding to their specific receptors, C3aR and C5aR, respectively [18].

Physical interactions of C5ar1

  • The inhibition of C5a binding to C5a receptor was studied using a radioligand binding assay [19].

Regulatory relationships of C5ar1


Other interactions of C5ar1

  • Airway hyperresponsiveness was substantially improved after C5aR blockade but not after C3aR blockade [13].
  • In this paper, we demonstrate that, in response to IgG immune complex formation, FcgammaRI/III- and C5aR-mediated pathways are both necessary and only together are they sufficient to trigger the full expression of inflammation in skin and lung [23].
  • Enhanced binding of C5a occurred, as well as increased mRNA for C5aR, after in vitro exposure of MDMEC to LPS, IFN-gamma, or IL-6 in a time- and dose-dependent manner [15].
  • Blocking the C5aR pathway by a specific C5a receptor antagonist (C5aRA) abrogated up-regulation of CXC chemokines but not of TNF-alpha and reduced neutrophil infiltration by >50% [11].
  • We found that renal expression of C5aR mRNA and protein was significantly increased in MRL/lpr mice compared to control MRL/+ mice [24].

Analytical, diagnostic and therapeutic context of C5ar1

  • Using the cecal ligation/puncture (CLP) model in mice, we show here that C5aR immunoreactivity was strikingly increased in lung, liver, kidney, and heart early in sepsis in both control and neutrophil-depleted mice [25].
  • Northern blot analysis of murine and baboon organs shows that, in addition to the liver, other tissues express C5aR mRNA in significant quantities, including the spleen, lung, heart, kidney, and intestine [20].
  • In vivo expression of C5aR in human liver cells was demonstrated by in situ hybridization and immunohistochemistry analyses [20].
  • HepG2 cells were demonstrated to express the C5aR on their cell surface by flow cytometric and immunofluorescence analyses as well as by 125I-C5a binding assays [20].
  • By confocal microscopy, C5aR could be detected on surfaces of MDMEC using anti-C5aR Ab [15].


  1. Macrophages induce the inflammatory response in the pulmonary Arthus reaction through G alpha i2 activation that controls C5aR and Fc receptor cooperation. Skokowa, J., Ali, S.R., Felda, O., Kumar, V., Konrad, S., Shushakova, N., Schmidt, R.E., Piekorz, R.P., Nürnberg, B., Spicher, K., Birnbaumer, L., Zwirner, J., Claassens, J.W., Verbeek, J.S., van Rooijen, N., Köhl, J., Gessner, J.E. J. Immunol. (2005) [Pubmed]
  2. The C5a chemoattractant receptor mediates mucosal defence to infection. Höpken, U.E., Lu, B., Gerard, N.P., Gerard, C. Nature (1996) [Pubmed]
  3. Impaired inflammatory responses in the reverse arthus reaction through genetic deletion of the C5a receptor. Höpken, U.E., Lu, B., Gerard, N.P., Gerard, C. J. Exp. Med. (1997) [Pubmed]
  4. Cloning and characterization of the guinea pig C5a anaphylatoxin receptor: interspecies diversity among the C5a receptors. Fukuoka, Y., Ember, J.A., Yasui, A., Hugli, T.E. Int. Immunol. (1998) [Pubmed]
  5. Complement factor 5 is a quantitative trait gene that modifies liver fibrogenesis in mice and humans. Hillebrandt, S., Wasmuth, H.E., Weiskirchen, R., Hellerbrand, C., Keppeler, H., Werth, A., Schirin-Sokhan, R., Wilkens, G., Geier, A., Lorenzen, J., Köhl, J., Gressner, A.M., Matern, S., Lammert, F. Nat. Genet. (2005) [Pubmed]
  6. Normal hematopoiesis and inflammatory responses despite discrete signaling defects in Galpha15 knockout mice. Davignon, I., Catalina, M.D., Smith, D., Montgomery, J., Swantek, J., Croy, J., Siegelman, M., Wilkie, T.M. Mol. Cell. Biol. (2000) [Pubmed]
  7. Distinct tissue site-specific requirements of mast cells and complement components C3/C5a receptor in IgG immune complex-induced injury of skin and lung. Baumann, U., Chouchakova, N., Gewecke, B., Köhl, J., Carroll, M.C., Schmidt, R.E., Gessner, J.E. J. Immunol. (2001) [Pubmed]
  8. Complement factor C5a exerts an anti-inflammatory effect in acute pancreatitis and associated lung injury. Bhatia, M., Saluja, A.K., Singh, V.P., Frossard, J.L., Lee, H.S., Bhagat, L., Gerard, C., Steer, M.L. Am. J. Physiol. Gastrointest. Liver Physiol. (2001) [Pubmed]
  9. Cell-derived anaphylatoxins as key mediators of antibody-dependent type II autoimmunity in mice. Kumar, V., Ali, S.R., Konrad, S., Zwirner, J., Verbeek, J.S., Schmidt, R.E., Gessner, J.E. J. Clin. Invest. (2006) [Pubmed]
  10. A regulatory role for the C5a anaphylatoxin in type 2 immunity in asthma. Köhl, J., Baelder, R., Lewkowich, I.P., Pandey, M.K., Hawlisch, H., Wang, L., Best, J., Herman, N.S., Sproles, A.A., Zwirner, J., Whitsett, J.A., Gerard, C., Sfyroera, G., Lambris, J.D., Wills-Karp, M. J. Clin. Invest. (2006) [Pubmed]
  11. Complement factor C5a mediates renal ischemia-reperfusion injury independent from neutrophils. de Vries, B., Köhl, J., Leclercq, W.K., Wolfs, T.G., van Bijnen, A.A., Heeringa, P., Buurman, W.A. J. Immunol. (2003) [Pubmed]
  12. C5a initiates the inflammatory cascade in immune complex peritonitis. Godau, J., Heller, T., Hawlisch, H., Trappe, M., Howells, E., Best, J., Zwirner, J., Verbeek, J.S., Hogarth, P.M., Gerard, C., Van Rooijen, N., Klos, A., Gessner, J.E., Köhl, J. J. Immunol. (2004) [Pubmed]
  13. Pharmacological targeting of anaphylatoxin receptors during the effector phase of allergic asthma suppresses airway hyperresponsiveness and airway inflammation. Baelder, R., Fuchs, B., Bautsch, W., Zwirner, J., Köhl, J., Hoymann, H.G., Glaab, T., Erpenbeck, V., Krug, N., Braun, A. J. Immunol. (2005) [Pubmed]
  14. On the role of complement and Fc gamma-receptors in the Arthus reaction. Köhl, J., Gessner, J.E. Mol. Immunol. (1999) [Pubmed]
  15. Expression and function of C5a receptor in mouse microvascular endothelial cells. Laudes, I.J., Chu, J.C., Huber-Lang, M., Guo, R.F., Riedemann, N.C., Sarma, J.V., Mahdi, F., Murphy, H.S., Speyer, C., Lu, K.T., Lambris, J.D., Zetoune, F.S., Ward, P.A. J. Immunol. (2002) [Pubmed]
  16. Airway hyper-reactivity mediated by B-1 cell immunoglobulin M antibody generating complement C5a at 1 day post-immunization in a murine hapten model of non-atopic asthma. Kawikova, I., Paliwal, V., Szczepanik, M., Itakura, A., Fukui, M., Campos, R.A., Geba, G.P., Homer, R.J., Iliopoulou, B.P., Pober, J.S., Tsuji, R.F., Askenase, P.W. Immunology (2004) [Pubmed]
  17. Structural diversity in the extracellular faces of peptidergic G-protein-coupled receptors. Molecular cloning of the mouse C5a anaphylatoxin receptor. Gerard, C., Bao, L., Orozco, O., Pearson, M., Kunz, D., Gerard, N.P. J. Immunol. (1992) [Pubmed]
  18. Expression of the complement anaphylatoxin C3a and C5a receptors on bronchial epithelial and smooth muscle cells in models of sepsis and asthma. Drouin, S.M., Kildsgaard, J., Haviland, J., Zabner, J., Jia, H.P., McCray, P.B., Tack, B.F., Wetsel, R.A. J. Immunol. (2001) [Pubmed]
  19. Pre-neutralization of C5a-mediated effects by the monoclonal antibody 137-26 reacting with the C5a moiety of native C5 without preventing C5 cleavage. Fung, M., Lu, M., Fure, H., Sun, W., Sun, C., Shi, N.Y., Dou, Y., Su, J., Swanson, X., Mollnes, T.E. Clin. Exp. Immunol. (2003) [Pubmed]
  20. Cellular expression of the C5a anaphylatoxin receptor (C5aR): demonstration of C5aR on nonmyeloid cells of the liver and lung. Haviland, D.L., McCoy, R.L., Whitehead, W.T., Akama, H., Molmenti, E.P., Brown, A., Haviland, J.C., Parks, W.C., Perlmutter, D.H., Wetsel, R.A. J. Immunol. (1995) [Pubmed]
  21. An anti-inflammatory function for the complement anaphylatoxin C5a-binding protein, C5L2. Gerard, N.P., Lu, B., Liu, P., Craig, S., Fujiwara, Y., Okinaga, S., Gerard, C. J. Biol. Chem. (2005) [Pubmed]
  22. Intracerebral complement C5a receptor (CD88) expression is regulated by TNF and lymphotoxin-alpha following closed head injury in mice. Stahel, P.F., Kariya, K., Shohami, E., Barnum, S.R., Eugster, H., Trentz, O., Kossmann, T., Morganti-Kossmann, M.C. J. Neuroimmunol. (2000) [Pubmed]
  23. A codominant role of Fc gamma RI/III and C5aR in the reverse Arthus reaction. Baumann, U., Köhl, J., Tschernig, T., Schwerter-Strumpf, K., Verbeek, J.S., Schmidt, R.E., Gessner, J.E. J. Immunol. (2000) [Pubmed]
  24. C5a promotes development of experimental lupus nephritis which can be blocked with a specific receptor antagonist. Bao, L., Osawe, I., Puri, T., Lambris, J.D., Haas, M., Quigg, R.J. Eur. J. Immunol. (2005) [Pubmed]
  25. Increased C5a receptor expression in sepsis. Riedemann, N.C., Guo, R.F., Neff, T.A., Laudes, I.J., Keller, K.A., Sarma, V.J., Markiewski, M.M., Mastellos, D., Strey, C.W., Pierson, C.L., Lambris, J.D., Zetoune, F.S., Ward, P.A. J. Clin. Invest. (2002) [Pubmed]
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