BioPAX pathway converted from "Anaphylatoxins initiate inflammatory responses" in the Reactome database.Anaphylatoxins initiate inflammatory responsesAnaphylatoxins initiate inflammatory responsesAnaphylatoxic peptides C3a and C5a function as mediators of host inflammatory response in mammals. These molecules are generated during complement activation and bind to their specific G protein coupled receptors (GPCR), which are expressed on granulocytes, monocytes, mast cells and activated lymphocytes (Peng Q et al. 2009; Haas PJ and van Strijp J 2007).<p>Expression of both C3 and C5 as well as C3aR and C5aR was detected in chicken liver and eye tissues (Haynes T et al. 2013). Moreover, chicken C3a was shown to stimulate chick retina regeneration through MAPK-STAT3 activation in a C3aR-dependent manner (Haynes T et al. 2013). In addition, functionally active anaphylatoxins and their receptors were found in teleost fish and Xenopus (Rottland J et al. 2004; Boshra H et al. 2004; Holland MC and Lambris JD 2004; Boshra H et al. 2005; Carmona-Fontaine C et al. 2011). The studies in those species suggested that the basic structure and function of anaphylatoxins and their receptors have been conserved for more than 300 million years (Sunyer JO et al. 2005). Taken together, the observations above suggest that the chicken complement signaling may release active fragments C3a and C5a, which associate with C3a and C5a receptors respectively. Authored: Shamovsky, V, 2012-12-20Reviewed: D'Eustachio, P, 2012-11-06Reviewed: Jupe, S, 2013-01-31Edited: Shamovsky, V, 2013-11-19C3a anaphylatoxin binds C3a receptorC3a anaphylatoxin binds C3a receptorIn mammals, complement C3a receptor (C3aR) is a member of the G protein-coupled receptor family (GPCRs) (Crass T et al. 1996). C3aR is activated upon binding of complement fragments C3a. C3aR transduces signals through multiple pathways, leading to the inhibition of adenylyl cyclase, activation of MAP kinase, phosphoinositol accumulation and calcium mobilization (Sayah S et al. 2003; Ricklin D et al. 2010).<p>Upon complement activation chicken C3 is cleaved into fragments that resemble mammalian C3a and C3b (Laursen I and Koch C 1989). Chicken C3 and its cleavage products were detected in liver, plasma and different eye tissues (Haynes T et al. 2013). In addition to C3 activation fragments, chicken C3aR mRNA and protein were found in eye tissues at E4 (embryo's stage at which retinectomies are performed). Histological analysis in combination with immuno-histochemical and western blotting procedures using post-retinectomy samples revealed that the treatment with chicken C3a induced chick retina regeneration via MAPK-STAT3 signaling in a C3aR-dependent manner (Haynes T et al. 2013).Authored: Shamovsky, V, 2012-12-20Reviewed: D'Eustachio, P, 2012-11-06Reviewed: Jupe, S, 2013-01-31Edited: Shamovsky, V, 2013-11-19Reactome DB_ID: 21321161extracellular regionGO0005576UniProt:Q90633 Complement C3Complement C3C3Reactomehttp://www.reactome.orgGallus gallusNCBI Taxonomy9031UniProtQ90633Chain Coordinates644EQUAL740EQUALReactome DB_ID: 21733121plasma membraneGO0005886UniProt:F1NMA7 C3AR1C3AR1SIMILARITY: Belongs to the G-protein coupled receptor 1 family.UniProtF1NMA7Reactome DB_ID: 21733301C3a:C3AR1 [plasma membrane]C3a:C3AR1Reactome DB_ID: 21321161644EQUAL740EQUALReactome DB_ID: 21733121Reactome Database ID Release 752173330Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2173330ReactomeR-GGA-21733301Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-2173330.1Reactome Database ID Release 752173317Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2173317ReactomeR-GGA-21733171Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-2173317.18765043Pubmed1996Expression cloning of the human C3a anaphylatoxin receptor (C3aR) from differentiated U-937 cellsCrass, TRaffetseder, UMartin, UGrove, MKlos, AKöhl, JBautsch, WEur J Immunol 26:1944-5023942241Pubmed2013Complement anaphylatoxin C3a is a potent inducer of embryonic chick retina regenerationHaynes, TracyLuz-Madrigal, AgustinReis, Edimara SEcheverri Ruiz, Nancy PGrajales-Esquivel, ErikaTzekou, ATsonis, Panagiotis ALambris, John DDel Rio-Tsonis, KatiaNat Commun 4:231220720586Pubmed2010Complement: a key system for immune surveillance and homeostasisRicklin, DHajishengallis, GYang, KLambris, JDNat Immunol 11:785-9712670702Pubmed2003Two different transduction pathways are activated by C3a and C5a anaphylatoxins on astrocytesSayah, SJauneau, ACPatte, CTonon, MCVaudry, HFontaine, MBrain Res Mol Brain Res 112:53-602587932Pubmed1989Purification of chicken C3 and a structural and functional characterizationLaursen, IKoch, CScand J Immunol 30:529-38C5a anaphylatoxin binds C5a receptorC5a anaphylatoxin binds C5a receptorIn mammals, complement C5a receptor (C5aR) is a member of the G protein-coupled receptor family (GPCRs) (Boulay et al. 1991; Gerard NP and Gerard C 1991). C5aR is activated upon binding of complement fragment C5a. C5aR transduces signals through multiple pathways, leading to the inhibition of adenylyl cyclase, activation of MAP kinase, phosphoinositol accumulation and calcium mobilization [Sayah S et al 2003; Ricklin D et al 2010; Wrann CD et al 2007].<p>Chicken C5aR mRNA was detected in liver and in various eye tissues (Haynes T et al. 2013). The binding of chicken C5a to C5aR has not been verified experimentally but is inferred from properties of the orthologous human proteins.Authored: Shamovsky, V, 2012-12-20Reviewed: D'Eustachio, P, 2012-11-06Reviewed: Jupe, S, 2013-01-31Edited: Shamovsky, V, 2013-11-19Reactome DB_ID: 21733701ENSEMBL:ENSGALP00000021731 C5aR1C5aR1ENSEMBLENSGALP00000021731Reactome DB_ID: 21322571UniProt:E1BRS7 Gga.27675Gga.27675SIMILARITY: Contains 1 NTR domain.UniProtE1BRS7679EQUAL757EQUALReactome DB_ID: 21733571C5a:C5AR1 [plasma membrane]C5a:C5AR1Reactome DB_ID: 21733701Reactome DB_ID: 21322571679EQUAL757EQUALReactome Database ID Release 752173357Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2173357ReactomeR-GGA-21733571Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-2173357.1Reactome Database ID Release 752173318Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2173318ReactomeR-GGA-21733181Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-2173318.12007135Pubmed1991Expression cloning of a receptor for C5a anaphylatoxin on differentiated HL-60 cellsBoulay, FMery, LTardif, MBrouchon, LVignais, PBiochemistry 30:2993-917507002Pubmed2007Distinct involvement of p38-, ERK1/2 and PKC signaling pathways in C5a-mediated priming of oxidative burst in phagocytic cellsWrann, CDWinter, SWBarkhausen, THildebrand, FKrettek, CRiedemann, NCCell Immunol 245:63-91847994Pubmed1991The chemotactic receptor for human C5a anaphylatoxinGerard, NPGerard, CNature 349:614-7Reactome Database ID Release 752173345Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2173345ReactomeR-GGA-21733451Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-2173345.115043949Pubmed2004Generation, purification and functional characterization of three C3a anaphylatoxins in rainbow trout: role in leukocyte chemotaxis and respiratory burstRotllant, JParra, DPeters, RBoshra, HSunyer, JODev Comp Immunol 28:815-2815034053Pubmed2004Cloning, expression, cellular distribution, and role in chemotaxis of a C5a receptor in rainbow trout: the first identification of a C5a receptor in a nonmammalian speciesBoshra, HLi, JPeters, RHansen, JMatlapudi, ASunyer, JOJ Immunol 172:4381-9022118769Pubmed2011Complement fragment C3a controls mutual cell attraction during collective cell migrationCarmona-Fontaine, CTheveneau, ETzekou, ATada, MWoods, MPage, KMParsons, MLambris, JDMayor, RDev Cell 21:1026-3716112742Pubmed2005Evolution of anaphylatoxins, their diversity and novel roles in innate immunity: insights from the study of fish complementSunyer, JOBoshra, HLi, JVet Immunol Immunopathol 108:77-8919601884Pubmed2009The role of anaphylatoxins C3a and C5a in regulating innate and adaptive immune responsesPeng, QLi, KSacks, SHZhou, WInflamm Allergy Drug Targets 8:236-4614688343Pubmed2004A functional C5a anaphylatoxin receptor in a teleost speciesHolland, MCLambris, JDJ Immunol 172:349-5516081814Pubmed2005Characterization of a C3a receptor in rainbow trout and Xenopus: the first identification of C3a receptors in nonmammalian speciesBoshra, HWang, THove-Madsen, LHansen, JLi, JMatlapudi, ASecombes, CJTort, LSunyer, JOJ Immunol 175:2427-3717873401Pubmed2007Anaphylatoxins: their role in bacterial infection and inflammationHaas, PJvan Strijp, JImmunol Res 37:161-75