C3a (complement)

The classical and alternative complement pathways.

C3a is one of the proteins formed by the cleavage of complement component 3; the other is C3b. C3a is a 77 residue anaphylatoxin that binds to the C3a receptor (C3aR), a class A G protein-coupled receptor. It plays a large role in the immune response.

C3a molecules induce responses through the GPCR C3a receptor. Like other anaphylatoxins, C3a is regulated by cleavage of its carboxy-terminal arginine, which results in a molecule with lowered inflammatory function (C3a desarginine).[1]

C3a is an effector of the complement system with a range of functions including T cell activation and survival,[2] angiogenesis stimulation,[3] chemotaxis, mast cell degranulation,[4] and macrophage activation.[5] It has been shown to have both proinflammatory and anti-inflammatory responses, its activity able to counteract the proinflammatory effects of C5a.[6]

Initial research in mice demonstrating an effective treatment after stroke is leading to further investigation to determine whether application to humans has potential.[7]

  1. ^ Cite error: The named reference :0 was invoked but never defined (see the help page).
  2. ^ Strainic, MG; Liu, J; Huang, D; An, F; Lalli, PN; Muqim, N; Shapiro, VS; Dubyak, GR; Heeger, PS; Medof, ME (March 2008). "Locally produced complement fragments C5a and C3a provide both costimulatory and survival signals to naive CD4+ T cells". Immunity. 28 (3): 425–35. doi:10.1016/j.immuni.2008.02.001. PMC 2646383. PMID 18328742.
  3. ^ Khan, MA; Assiri, AM; Broering, DC (22 July 2015). "Complement and macrophage crosstalk during process of angiogenesis in tumor progression". Journal of Biomedical Science. 22 (1): 58. doi:10.1186/s12929-015-0151-1. PMC 4511526. PMID 26198107.
  4. ^ Reid, Robert C.; Yau, Mei-Kwan; Singh, Ranee; Hamidon, Johan K.; Reed, Anthony N.; Chu, Peifei; Suen, Jacky Y.; Stoermer, Martin J.; Blakeney, Jade S.; Lim, Junxian; Faber, Jonathan M.; Fairlie, David P. (21 November 2013). "Downsizing a human inflammatory protein to a small molecule with equal potency and functionality". Nature Communications. 4 (1): 2802. Bibcode:2013NatCo...4.2802R. doi:10.1038/ncomms3802. ISSN 2041-1723. PMID 24257095. S2CID 5465825.
  5. ^ Mathern, DR; Heeger, PS (4 September 2015). "Molecules Great and Small: The Complement System". Clinical Journal of the American Society of Nephrology. 10 (9): 1636–50. doi:10.2215/cjn.06230614. PMC 4559511. PMID 25568220.
  6. ^ Coulthard, LG; Woodruff, TM (15 April 2015). "Is the complement activation product C3a a proinflammatory molecule? Re-evaluating the evidence and the myth". Journal of Immunology. 194 (8): 3542–8. doi:10.4049/jimmunol.1403068. PMID 25848071.
  7. ^ Anna Stokowska, Markus Aswendt, Daniel Zucha, Stephanie Lohmann, Frederique Wieters, Javier Morán Suarez, Alison L. Atkins, YiXian Li, Maria Miteva, Julia Lewin, Dirk Wiedermann, Michael Diedenhofen, Åsa Torinsson Naluai, Pavel Abaffy, Lukas Valihrach, Mikael Kubista, Mathias Hoehn, Milos Pekny, and Marcela Pekna, Complement C3a treatment accelerates recovery after stroke via modulation of astrocyte reactivity and cortical connectivity, Journal of Clinical Investigation, March 30, 2023