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C5  -  complement component 5

Rattus norvegicus

Synonyms: C5a, Complement C5, Hc, RGD1561905
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Disease relevance of C5


Psychiatry related information on C5

  • Clinical studies over the past several years have correlated the use of anti-inflammatory drugs with a decrease in the incidence and progression of AD dementia and/or dysfunction, supporting a role for gliosis and inflammation in AD pathogenesis (reviewed in ref. 6). C5a, a product of C' activation, is chemotactic for microglia [6].

High impact information on C5

  • These data indicate that sepsis causes an excessive production of C5a, which compromises the bactericidal function of neutrophils [7].
  • Blood neutrophils from these rats contained on their surfaces the powerful complement activation product C5a [7].
  • Protective effects of C5a blockade in sepsis [7].
  • In contrast, when companion CLP rats were treated with IgG antibody against C5a, survival rates were significantly improved, levels of bacteremia were considerably reduced, and the H2O2 response of blood neutrophils was preserved [7].
  • Bacterial colony-forming units in spleen and liver were very high in CLP rats treated with preimmune IgG and very low in CLP rats treated with IgG antibody against C5a, similar to values obtained in rats that underwent 'sham' operations (without CLP) [7].

Chemical compound and disease context of C5


Biological context of C5


Anatomical context of C5

  • Correspondingly, it was found that hepatocytes, in contrast to Kupffer cells, did not express C5a receptors [15].
  • At this time-point, C5a directly activated glycogen phosphorylase in isolated hepatocytes and enhanced glucose output in perfused livers without the involvement of prostanoids [15].
  • Anaphylatoxin C5a receptor mRNA is strongly expressed in Kupffer and stellate cells and weakly in sinusoidal endothelial cells but not in hepatocytes of normal rat liver [11].
  • The liver can be a primary target organ for the C5a anaphylatoxin since the liver is directly connected to the gut, via the mesenteric veins and portal vein which is a main source of complement activating lipopolysaccharides (LPS) [16].
  • Growing evidence obtained in recent years indicates that anaphylatoxin C5a receptors (C5aR) are not restricted to myeloid cells but are also expressed on nonmyeloid cells in different tissues such as brain, lung, skin and liver [16].

Associations of C5 with chemical compounds


Physical interactions of C5

  • However, little is known about the role of the C5a/C5aR complex in liver and its involvement during a proliferative process [18].

Regulatory relationships of C5

  • CONCLUSIONS: Thus, IL-6 from Kupffer cells appears to be the main mediator of LPS-induced de novo expression of C5a receptors in hepatocytes [15].
  • Activation of the complement system generates the anaphylatoxin C5a whose activities are mediated through its binding to the widely expressed C5aR [18].
  • Monocyte-macrophages from animals treated with IFN-gamma exhibited defective chemotactic responses when tested in vitro and furthermore, monocytes cultured with IFN-gamma (25 to 500 U/ml) in vitro had significantly suppressed chemotactic responses to the complement fragment C5a (p less than 0.005) [19].

Other interactions of C5


Analytical, diagnostic and therapeutic context of C5

  • Immunohistochemistry demonstrated prominent phosphorylated (p) inhibitory factor-kappaB (IkappaB)-alpha staining of intestinal tissue after GI/R, whereas anti-C5 reduced p-IkappaB-alpha expression [20].
  • However, a significantly increased expression of cyclin E and D1mRNA levels, as well as an increased BrdU incorporation, were observed in rats given an i.v. C5a agonist injection following an 80% partial hepatectomy [18].
  • Insertion of residues LLH between Gln-3 and Lys-4 in a recombinant human C5a molecule using site-directed mutagenesis failed to enhance potency [17].
  • Pep-A bound to PL37 and to C5a with very slow dissociation as determined by analysis using surface plasmon resonance, whereas Pep-B failed to bind at all [21].
  • BACKGROUND: C5a has been implicated in numerous pathophysiological conditions, including ischemia/reperfusion (I/R) injury of the kidney [22].


  1. Expression and induction of anaphylatoxin C5a receptors in the rat liver. Schlaf, G., Schmitz, M., Rothermel, E., Jungermann, K., Schieferdecker, H.L., Götze, O. Histol. Histopathol. (2003) [Pubmed]
  2. Anaphylatoxin C5a actions in rat liver: synergistic enhancement by C5a of lipopolysaccharide-dependent alpha(2)-macroglobulin gene expression in hepatocytes via IL-6 release from Kupffer cells. Mäck, C., Jungermann, K., Götze, O., Schieferdecker, H.L. J. Immunol. (2001) [Pubmed]
  3. Experimental diffuse axonal injury induces enhanced neuronal C5a receptor mRNA expression in rats. Stahel, P.F., Kossmann, T., Morganti-Kossmann, M.C., Hans, V.H., Barnum, S.R. Brain Res. Mol. Brain Res. (1997) [Pubmed]
  4. A new small molecule C5a receptor antagonist inhibits the reverse-passive Arthus reaction and endotoxic shock in rats. Strachan, A.J., Woodruff, T.M., Haaima, G., Fairlie, D.P., Taylor, S.M. J. Immunol. (2000) [Pubmed]
  5. Antiarthritic activity of an orally active C5a receptor antagonist against antigen-induced monarticular arthritis in the rat. Woodruff, T.M., Strachan, A.J., Dryburgh, N., Shiels, I.A., Reid, R.C., Fairlie, D.P., Taylor, S.M. Arthritis Rheum. (2002) [Pubmed]
  6. Aspartate residue 7 in amyloid beta-protein is critical for classical complement pathway activation: implications for Alzheimer's disease pathogenesis. Velazquez, P., Cribbs, D.H., Poulos, T.L., Tenner, A.J. Nat. Med. (1997) [Pubmed]
  7. Protective effects of C5a blockade in sepsis. Czermak, B.J., Sarma, V., Pierson, C.L., Warner, R.L., Huber-Lang, M., Bless, N.M., Schmal, H., Friedl, H.P., Ward, P.A. Nat. Med. (1999) [Pubmed]
  8. Inhibition of C5 or absence of C6 protects from sepsis mortality. Buras, J.A., Rice, L., Orlow, D., Pavlides, S., Reenstra, W.R., Ceonzo, K., Stahl, G.L. Immunobiology (2004) [Pubmed]
  9. The role of the polymorphonuclear leukocyte in hyperalgesia. Levine, J.D., Gooding, J., Donatoni, P., Borden, L., Goetzl, E.J. J. Neurosci. (1985) [Pubmed]
  10. Roles of histamine, complement and xanthine oxidase in thermal injury of skin. Friedl, H.P., Till, G.O., Trentz, O., Ward, P.A. Am. J. Pathol. (1989) [Pubmed]
  11. Anaphylatoxin C5a receptor mRNA is strongly expressed in Kupffer and stellate cells and weakly in sinusoidal endothelial cells but not in hepatocytes of normal rat liver. Schieferdecker, H.L., Rothermel, E., Timmermann, A., Götze, O., Jungermann, K. FEBS Lett. (1997) [Pubmed]
  12. Nucleotide and corrected amino acid sequence of the functional recombinant rat anaphylatoxin C5a. Rothermel, E., Rolf, O., Götze, O., Zwirner, J. Biochim. Biophys. Acta (1997) [Pubmed]
  13. Characterization of C3a and C5a receptors in rat cerebellar granule neurons during maturation. Neuroprotective effect of C5a against apoptotic cell death. Bénard, M., Gonzalez, B.J., Schouft, M.T., Falluel-Morel, A., Vaudry, D., Chan, P., Vaudry, H., Fontaine, M. J. Biol. Chem. (2004) [Pubmed]
  14. Cross-desensitization of chemoattractant receptors occurs at multiple levels. Evidence for a role for inhibition of phospholipase C activity. Richardson, R.M., Ali, H., Tomhave, E.D., Haribabu, B., Snyderman, R. J. Biol. Chem. (1995) [Pubmed]
  15. Induction of anaphylatoxin C5a receptors in rat hepatocytes by lipopolysaccharide in vivo: mediation by interleukin-6 from Kupffer cells. Koleva, M., Schlaf, G., Landmann, R., Götze, O., Jungermann, K., Schieferdecker, H.L. Gastroenterology (2002) [Pubmed]
  16. Functions of anaphylatoxin C5a in rat liver: direct and indirect actions on nonparenchymal and parenchymal cells. Schieferdecker, H.L., Schlaf, G., Jungermann, K., Götze, O. Int. Immunopharmacol. (2001) [Pubmed]
  17. Primary structure and functional characterization of rat C5a: an anaphylatoxin with unusually high potency. Cui, L., Carney, D.F., Hugli, T.E. Protein Sci. (1994) [Pubmed]
  18. Expression of a functional C5a receptor in regenerating hepatocytes and its involvement in a proliferative signaling pathway in rat. Daveau, M., Benard, M., Scotte, M., Schouft, M.T., Hiron, M., Francois, A., Salier, J.P., Fontaine, M. J. Immunol. (2004) [Pubmed]
  19. IFN-gamma inhibits inflammatory cell recruitment and the evolution of bacterial cell wall-induced arthritis. Wahl, S.M., Allen, J.B., Ohura, K., Chenoweth, D.E., Hand, A.R. J. Immunol. (1991) [Pubmed]
  20. Role for complement in mediating intestinal nitric oxide synthase-2 and superoxide dismutase expression. Montalto, M.C., Hart, M.L., Jordan, J.E., Wada, K., Stahl, G.L. Am. J. Physiol. Gastrointest. Liver Physiol. (2003) [Pubmed]
  21. Inactivation of C5a anaphylatoxin by a peptide that is complementary to a region of C5a. Fujita, E., Farkas, I., Campbell, W., Baranyi, L., Okada, H., Okada, N. J. Immunol. (2004) [Pubmed]
  22. A small molecule C5a receptor antagonist protects kidneys from ischemia/reperfusion injury in rats. Arumugam, T.V., Shiels, I.A., Strachan, A.J., Abbenante, G., Fairlie, D.P., Taylor, S.M. Kidney Int. (2003) [Pubmed]
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