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C3a (complement)

December 15, 2023

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.

The classical and alternative complement pathways.

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]

Structure edit

C3a edit

C3a is a strongly basic and highly cationic 77 residue protein with a molecular mass of approximately 10 kDa.[8] Residues 17-66 are made up of three anti-parallel helices and three disulfide bonds, which confer stability to the protein. The N-terminus consists of a fourth flexible helical structure, while the C terminus is disordered.[9] C3a has a regulatory process and a structure homologous to complement component C5a, with which it shares 36% of its sequence identity.[1]

Receptor edit

C3a induces an immunological response through a 482 residue G-protein-coupled receptor called C3a receptor (C3aR). The C3aR is similarly structurally homologous to C5aR, but contains an extracellular domain with more than 160 amino acids.[10] Specific binding sites for interactions between C3a and C3aR are unknown, but it has been shown that sulfation of tyrosine 174, one of the amino acids in the extracellular domain, is required for C3a binding.[11] It has also been demonstrated that the C3aR N terminus is not required for ligand binding.[12]

Formation edit

C3a formation occurs through activation and cleavage of complement component 3 in a reaction catalyzed by C3-convertase. There are three pathways of activation, each of which leads to the formation of C3a and C3b, which is involved in antigen opsonization. Other than the alternative pathway, which is constantly active, C3a formation is triggered by pathogenic infection.

Classical pathway edit

The classical pathway of complement activation is initiated when the C1 complex, made up of C1r and C1s serine proteases, recognizes the Fc region of IgM or IgG antibodies bound to a pathogen. C1q mediates the classical pathway by activating the C1 complex, which cleaves C4 and C2 into smaller fragments (C4a, C4b, C2a, and C2b). C4a and C2b form C4bC2b, also known as C3 convertase.[13]

Lectin pathway edit

The lectin pathway is activated when pattern-recognition receptors, like mannan-binding lectin or ficolins, recognize and bind to pathogen-associated molecular patterns on the antigen, including sugars.[14] These bound receptors then complex with Mannose-Binding Lectin-Associated Serine Proteases (MASPs), which have proteolytic activity similar to the C1 complex. The MASPs cleave C4 and C2, resulting in C3 convertase formation.[15]

Alternative pathway edit

The alternative pathway of complement activation is typically always active at low levels in blood plasma through a process called tick-over, in which C3 spontaneously hydrolyzes into its active form, C3(H2O). This activation induces a conformational change in the thioester domain of C3(H2O) that allows it to bind to a plasma protein called Factor B. This complex is then cleaved by Factor D, a serine protease, to form C3b(H2O)Bb, or fluid-phase C3-convertase. This complex has the ability to catalyze the formation of C3a and C3b after it binds properdin, a globulin protein, and is stabilized.[16]

Functions edit

Anaphylatoxins are small complement peptides that induce proinflammatory responses in tissues. C3a is primarily regarded for its role in the innate and adaptive immune responses as an anaphylatoxin, moderating and activating multiple inflammatory pathways.

Role in innate immunity edit

The roles of C3a in innate immunity, upon binding C3aR, include increased vasodilation via endothelial cell contraction, increased vascular permeability, and mast cell and basophil degranulation of histamine, induction of respiratory burst and subsequent degradation of pathogens by neutrophils, macrophages, and eosinophils, and regulation of cationic eosinophil protein migration, adhesion, and production.[17] C3a is also able to play a role in chemotaxis for mast cells and eosinophils, but C5a is a more potent chemoattractant.[18]

Traditionally thought to serve a strictly pro-inflammatory role, recent investigations have shown that C3a can also work against C5a to serve an anti-inflammatory role. In addition, migration and degranulation of neutrophils can be suppressed in the presence of C3a.[6]

Role in adaptive immunity edit

C3a also plays an important role in adaptive immunity, moderating leukocyte production and proliferation. C3a is able to regulate B cell and monocyte production of IL-6 and TNF-α, and human C3a has been shown to dampen the polyclonal immune response through dose-dependent regulation of B cell molecule production.[19] C3aR signaling along antigen-presenting cells' CD28 and CD40L pathways also plays a role in T cell proliferation and differentiation.[2] C3aR has been shown to be necessary for TH1 cell generation and regulates TH1 IL-10 expression, while an absence of active C3aR on dendritic cells upregulates regulatory T cell production. The absence of C3 has also been shown to decrease IL-2 receptor expression on T cells.[19]

Regulation edit

Regulation of complement activation edit

Levels of complement are regulated by moderating convertase formation and enzymatic activity. C3 convertase formation is primarily regulated by levels of active C3b and C4b. Factor I, a serine protease activated by cofactors, can cleave and C3b and C4b, thus preventing convertase formation. C3 convertase activity is also regulated without C3b inactivation, through complement control proteins, including decay-accelerating factors that function to speed up C3 convertase half-lives and avert convertase formation.[14]

Deactivation edit

C3a, like other anaphylatoxins, has a C-terminal arginine residue. Serum carboxypeptidase B, a protease, cleaves the arginine residue from C3a, forming the desArg derivative of C3a, also known as acylation stimulating protein (ASP). Unlike C5a desArg, this version of C3a has no proinflammatory activity.[1] However, ASP functions as a hormone in the adipose tissue, moderating fatty acid migration to adipocytes and triacylglycerol synthesis.[20] In addition, it has been shown that ASP downregulates the polyclonal immune response in the same way C3a does.[14]

References edit

  1. ^ a b c Bajic, Goran; Yatime, Laure; Klos, Andreas; Andersen, Gregers Rom (2013-02-01). "Human C3a and C3a desArg anaphylatoxins have conserved structures, in contrast to C5a and C5a desArg". Protein Science. 22 (2): 204–212. doi:10.1002/pro.2200. ISSN 1469-896X. PMC 3588916. PMID 23184394.
  2. ^ a b 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. ^ a b 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
  8. ^ Zhou, Wuding (2012-02-01). "The new face of anaphylatoxins in immune regulation". Immunobiology. 217 (2): 225–234. doi:10.1016/j.imbio.2011.07.016. ISSN 1878-3279. PMID 21856033.
  9. ^ Chang, Jui-Yoa; Lin, Curtis C. -J.; Salamanca, Silvia; Pangburn, Michael K.; Wetsel, Rick A. (2008-12-15). "Denaturation and unfolding of human anaphylatoxin C3a: An unusually low covalent stability of its native disulfide bonds". Archives of Biochemistry and Biophysics. 480 (2): 104–110. doi:10.1016/j.abb.2008.09.013. PMC 2636726. PMID 18854167.
  10. ^ Ames, R. S.; Li, Y.; Sarau, H. M.; Nuthulaganti, P.; Foley, J. J.; Ellis, C.; Zeng, Z.; Su, K.; Jurewicz, A. J. (1996-08-23). "Molecular cloning and characterization of the human anaphylatoxin C3a receptor". The Journal of Biological Chemistry. 271 (34): 20231–20234. doi:10.1074/jbc.271.34.20231. ISSN 0021-9258. PMID 8702752.
  11. ^ Gao, Jinming; Choe, Hyeryun; Bota, Dalena; Wright, Paulette L.; Gerard, Craig; Gerard, Norma P. (2003-09-26). "Sulfation of tyrosine 174 in the human C3a receptor is essential for binding of C3a anaphylatoxin". The Journal of Biological Chemistry. 278 (39): 37902–37908. doi:10.1074/jbc.M306061200. ISSN 0021-9258. PMID 12871936.
  12. ^ Crass, T.; Ames, R. S.; Sarau, H. M.; Tornetta, M. A.; Foley, J. J.; Köhl, J.; Klos, A.; Bautsch, W. (1999-03-26). "Chimeric receptors of the human C3a receptor and C5a receptor (CD88)". The Journal of Biological Chemistry. 274 (13): 8367–8370. doi:10.1074/jbc.274.13.8367. ISSN 0021-9258. PMID 10085065.
  13. ^ Arlaud, G. J.; Gaboriaud, C.; Thielens, N. M.; Rossi, V.; Bersch, B.; Hernandez, J. F.; Fontecilla-Camps, J. C. (2001-04-01). "Structural biology of C1: dissection of a complex molecular machinery". Immunological Reviews. 180: 136–145. doi:10.1034/j.1600-065x.2001.1800112.x. ISSN 0105-2896. PMID 11414355. S2CID 21136630.
  14. ^ a b c Dunkelberger, Jason R.; Song, Wen-Chao (2010-01-01). "Complement and its role in innate and adaptive immune responses". Cell Research. 20 (1): 34–50. doi:10.1038/cr.2009.139. ISSN 1748-7838. PMID 20010915.
  15. ^ Degn, Søren E.; Thiel, Steffen; Jensenius, Jens C. (2007-01-01). "New perspectives on mannan-binding lectin-mediated complement activation". Immunobiology. 212 (4–5): 301–311. doi:10.1016/j.imbio.2006.12.004. ISSN 0171-2985. PMID 17544815.
  16. ^ Merle, Nicolas S.; Church, Sarah Elizabeth; Fremeaux-Bacchi, Veronique; Roumenina, Lubka T. (2015-01-01). "Complement System Part I - Molecular Mechanisms of Activation and Regulation". Frontiers in Immunology. 6: 262. doi:10.3389/fimmu.2015.00262. ISSN 1664-3224. PMC 4451739. PMID 26082779.
  17. ^ Klos, Andreas; Tenner, Andrea J.; Johswich, Kay-Ole; Ager, Rahasson R.; Reis, Edimara S.; Köhl, Jörg (2009-09-01). "The role of the anaphylatoxins in health and disease". Molecular Immunology. 12th European Meeting on Complement in Human Disease12th European Meeting on CHD12th European Meeting on Complement in Human Disease. 46 (14): 2753–2766. doi:10.1016/j.molimm.2009.04.027. PMC 2725201. PMID 19477527.
  18. ^ Schraufstatter, Ingrid U.; DiScipio, Richard G.; Zhao, Ming; Khaldoyanidi, Sophia K. (2009-03-15). "C3a and C5a Are Chemotactic Factors for Human Mesenchymal Stem Cells, Which Cause Prolonged ERK1/2 Phosphorylation". The Journal of Immunology. 182 (6): 3827–3836. doi:10.4049/jimmunol.0803055. ISSN 0022-1767. PMID 19265162.
  19. ^ a b Merle, Nicolas S.; Noe, Remi; Halbwachs-Mecarelli, Lise; Fremeaux-Bacchi, Veronique; Roumenina, Lubka T. (2015-05-26). "Complement System Part II: Role in Immunity". Frontiers in Immunology. 6: 257. doi:10.3389/fimmu.2015.00257. ISSN 1664-3224. PMC 4443744. PMID 26074922.
  20. ^ Barbu, Andreea; Hamad, Osama A.; Lind, Lars; Ekdahl, Kristina N.; Nilsson, Bo (2015-09-01). "The role of complement factor C3 in lipid metabolism". Molecular Immunology. 15th European Meeting on Complement in Human Disease 2015, Uppsala, Sweden. 67 (1): 101–107. doi:10.1016/j.molimm.2015.02.027. PMID 25746915.
  • Dinasarapu, A R; Chandrasekhar, A; Sahu, A; Subramaniam, S (2012). "Complement C3 (Human)". UCSD Molecule Pages (2). doi:10.6072/H0.MP.A004235.01.

External links edit

December 15, 2023
complement, proteins, formed, cleavage, complement, component, other, residue, anaphylatoxin, that, binds, receptor, c3ar, class, protein, coupled, receptor, plays, large, role, immune, response, classical, alternative, complement, pathways, molecules, induce,. 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 The classical and alternative complement pathways 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 Contents 1 Structure 1 1 C3a 1 2 Receptor 2 Formation 2 1 Classical pathway 2 2 Lectin pathway 2 3 Alternative pathway 3 Functions 3 1 Role in innate immunity 3 2 Role in adaptive immunity 4 Regulation 4 1 Regulation of complement activation 4 2 Deactivation 5 References 6 External linksStructure editC3a edit C3a is a strongly basic and highly cationic 77 residue protein with a molecular mass of approximately 10 kDa 8 Residues 17 66 are made up of three anti parallel helices and three disulfide bonds which confer stability to the protein The N terminus consists of a fourth flexible helical structure while the C terminus is disordered 9 C3a has a regulatory process and a structure homologous to complement component C5a with which it shares 36 of its sequence identity 1 Receptor edit C3a induces an immunological response through a 482 residue G protein coupled receptor called C3a receptor C3aR The C3aR is similarly structurally homologous to C5aR but contains an extracellular domain with more than 160 amino acids 10 Specific binding sites for interactions between C3a and C3aR are unknown but it has been shown that sulfation of tyrosine 174 one of the amino acids in the extracellular domain is required for C3a binding 11 It has also been demonstrated that the C3aR N terminus is not required for ligand binding 12 Formation editC3a formation occurs through activation and cleavage of complement component 3 in a reaction catalyzed by C3 convertase There are three pathways of activation each of which leads to the formation of C3a and C3b which is involved in antigen opsonization Other than the alternative pathway which is constantly active C3a formation is triggered by pathogenic infection Classical pathway edit The classical pathway of complement activation is initiated when the C1 complex made up of C1r and C1s serine proteases recognizes the Fc region of IgM or IgG antibodies bound to a pathogen C1q mediates the classical pathway by activating the C1 complex which cleaves C4 and C2 into smaller fragments C4a C4b C2a and C2b C4a and C2b form C4bC2b also known as C3 convertase 13 Lectin pathway edit The lectin pathway is activated when pattern recognition receptors like mannan binding lectin or ficolins recognize and bind to pathogen associated molecular patterns on the antigen including sugars 14 These bound receptors then complex with Mannose Binding Lectin Associated Serine Proteases MASPs which have proteolytic activity similar to the C1 complex The MASPs cleave C4 and C2 resulting in C3 convertase formation 15 Alternative pathway edit The alternative pathway of complement activation is typically always active at low levels in blood plasma through a process called tick over in which C3 spontaneously hydrolyzes into its active form C3 H2O This activation induces a conformational change in the thioester domain of C3 H2O that allows it to bind to a plasma protein called Factor B This complex is then cleaved by Factor D a serine protease to form C3b H2O Bb or fluid phase C3 convertase This complex has the ability to catalyze the formation of C3a and C3b after it binds properdin a globulin protein and is stabilized 16 Functions editAnaphylatoxins are small complement peptides that induce proinflammatory responses in tissues C3a is primarily regarded for its role in the innate and adaptive immune responses as an anaphylatoxin moderating and activating multiple inflammatory pathways Role in innate immunity edit The roles of C3a in innate immunity upon binding C3aR include increased vasodilation via endothelial cell contraction increased vascular permeability and mast cell and basophil degranulation of histamine induction of respiratory burst and subsequent degradation of pathogens by neutrophils macrophages and eosinophils and regulation of cationic eosinophil protein migration adhesion and production 17 C3a is also able to play a role in chemotaxis for mast cells and eosinophils but C5a is a more potent chemoattractant 18 Traditionally thought to serve a strictly pro inflammatory role recent investigations have shown that C3a can also work against C5a to serve an anti inflammatory role In addition migration and degranulation of neutrophils can be suppressed in the presence of C3a 6 Role in adaptive immunity edit C3a also plays an important role in adaptive immunity moderating leukocyte production and proliferation C3a is able to regulate B cell and monocyte production of IL 6 and TNF a and human C3a has been shown to dampen the polyclonal immune response through dose dependent regulation of B cell molecule production 19 C3aR signaling along antigen presenting cells CD28 and CD40L pathways also plays a role in T cell proliferation and differentiation 2 C3aR has been shown to be necessary for TH1 cell generation and regulates TH1 IL 10 expression while an absence of active C3aR on dendritic cells upregulates regulatory T cell production The absence of C3 has also been shown to decrease IL 2 receptor expression on T cells 19 Regulation editRegulation of complement activation edit Levels of complement are regulated by moderating convertase formation and enzymatic activity C3 convertase formation is primarily regulated by levels of active C3b and C4b Factor I a serine protease activated by cofactors can cleave and C3b and C4b thus preventing convertase formation C3 convertase activity is also regulated without C3b inactivation through complement control proteins including decay accelerating factors that function to speed up C3 convertase half lives and avert convertase formation 14 Deactivation edit C3a like other anaphylatoxins has a C terminal arginine residue Serum carboxypeptidase B a protease cleaves the arginine residue from C3a forming the desArg derivative of C3a also known as acylation stimulating protein ASP Unlike C5a desArg this version of C3a has no proinflammatory activity 1 However ASP functions as a hormone in the adipose tissue moderating fatty acid migration to adipocytes and triacylglycerol synthesis 20 In addition it has been shown that ASP downregulates the polyclonal immune response in the same way C3a does 14 References edit a b c Bajic Goran Yatime Laure Klos Andreas Andersen Gregers Rom 2013 02 01 Human C3a and C3a desArg anaphylatoxins have conserved structures in contrast to C5a and C5a desArg Protein Science 22 2 204 212 doi 10 1002 pro 2200 ISSN 1469 896X PMC 3588916 PMID 23184394 a b 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 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 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 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 a b 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 Anna Stokowska Markus Aswendt Daniel Zucha Stephanie Lohmann Frederique Wieters Javier Moran Suarez Alison L Atkins YiXian Li Maria Miteva Julia Lewin Dirk Wiedermann Michael Diedenhofen Asa 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 Zhou Wuding 2012 02 01 The new face of anaphylatoxins in immune regulation Immunobiology 217 2 225 234 doi 10 1016 j imbio 2011 07 016 ISSN 1878 3279 PMID 21856033 Chang Jui Yoa Lin Curtis C J Salamanca Silvia Pangburn Michael K Wetsel Rick A 2008 12 15 Denaturation and unfolding of human anaphylatoxin C3a An unusually low covalent stability of its native disulfide bonds Archives of Biochemistry and Biophysics 480 2 104 110 doi 10 1016 j abb 2008 09 013 PMC 2636726 PMID 18854167 Ames R S Li Y Sarau H M Nuthulaganti P Foley J J Ellis C Zeng Z Su K Jurewicz A J 1996 08 23 Molecular cloning and characterization of the human anaphylatoxin C3a receptor The Journal of Biological Chemistry 271 34 20231 20234 doi 10 1074 jbc 271 34 20231 ISSN 0021 9258 PMID 8702752 Gao Jinming Choe Hyeryun Bota Dalena Wright Paulette L Gerard Craig Gerard Norma P 2003 09 26 Sulfation of tyrosine 174 in the human C3a receptor is essential for binding of C3a anaphylatoxin The Journal of Biological Chemistry 278 39 37902 37908 doi 10 1074 jbc M306061200 ISSN 0021 9258 PMID 12871936 Crass T Ames R S Sarau H M Tornetta M A Foley J J Kohl J Klos A Bautsch W 1999 03 26 Chimeric receptors of the human C3a receptor and C5a receptor CD88 The Journal of Biological Chemistry 274 13 8367 8370 doi 10 1074 jbc 274 13 8367 ISSN 0021 9258 PMID 10085065 Arlaud G J Gaboriaud C Thielens N M Rossi V Bersch B Hernandez J F Fontecilla Camps J C 2001 04 01 Structural biology of C1 dissection of a complex molecular machinery Immunological Reviews 180 136 145 doi 10 1034 j 1600 065x 2001 1800112 x ISSN 0105 2896 PMID 11414355 S2CID 21136630 a b c Dunkelberger Jason R Song Wen Chao 2010 01 01 Complement and its role in innate and adaptive immune responses Cell Research 20 1 34 50 doi 10 1038 cr 2009 139 ISSN 1748 7838 PMID 20010915 Degn Soren E Thiel Steffen Jensenius Jens C 2007 01 01 New perspectives on mannan binding lectin mediated complement activation Immunobiology 212 4 5 301 311 doi 10 1016 j imbio 2006 12 004 ISSN 0171 2985 PMID 17544815 Merle Nicolas S Church Sarah Elizabeth Fremeaux Bacchi Veronique Roumenina Lubka T 2015 01 01 Complement System Part I Molecular Mechanisms of Activation and Regulation Frontiers in Immunology 6 262 doi 10 3389 fimmu 2015 00262 ISSN 1664 3224 PMC 4451739 PMID 26082779 Klos Andreas Tenner Andrea J Johswich Kay Ole Ager Rahasson R Reis Edimara S Kohl Jorg 2009 09 01 The role of the anaphylatoxins in health and disease Molecular Immunology 12th European Meeting on Complement in Human Disease12th European Meeting on CHD12th European Meeting on Complement in Human Disease 46 14 2753 2766 doi 10 1016 j molimm 2009 04 027 PMC 2725201 PMID 19477527 Schraufstatter Ingrid U DiScipio Richard G Zhao Ming Khaldoyanidi Sophia K 2009 03 15 C3a and C5a Are Chemotactic Factors for Human Mesenchymal Stem Cells Which Cause Prolonged ERK1 2 Phosphorylation The Journal of Immunology 182 6 3827 3836 doi 10 4049 jimmunol 0803055 ISSN 0022 1767 PMID 19265162 a b Merle Nicolas S Noe Remi Halbwachs Mecarelli Lise Fremeaux Bacchi Veronique Roumenina Lubka T 2015 05 26 Complement System Part II Role in Immunity Frontiers in Immunology 6 257 doi 10 3389 fimmu 2015 00257 ISSN 1664 3224 PMC 4443744 PMID 26074922 Barbu Andreea Hamad Osama A Lind Lars Ekdahl Kristina N Nilsson Bo 2015 09 01 The role of complement factor C3 in lipid metabolism Molecular Immunology 15th European Meeting on Complement in Human Disease 2015 Uppsala Sweden 67 1 101 107 doi 10 1016 j molimm 2015 02 027 PMID 25746915 Dinasarapu A R Chandrasekhar A Sahu A Subramaniam S 2012 Complement C3 Human UCSD Molecule Pages 2 doi 10 6072 H0 MP A004235 01 External links edithttp www merck com mmpe sec13 ch163 ch163d html Retrieved from https en wikipedia org w index php title C3a complement amp oldid 1189379183, wikipedia, wiki, book, books, library,

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