title: Is the complement activation product C3a a proinflammatory molecule? Re-evaluating the evidence and the myth.
abstract: The complement activation product C3a is often described as a proinflammatory mediator, alongside its downstream cousin, C5a. However, emerging studies show that C3a has several anti-inflammatory facets in vivo. For example, in the acute inflammatory response, C3a acts in direct opposition to C5a, through preventing the accumulation of neutrophils in inflamed tissues by independently regulating their mobilization. This acute, protective, and opposing activity of C3a to C5a is also illustrated in models of septicemia. In this article, we reinvestigate the discovery and original classification of C3a as a proinflammatory mediator and highlight the emerging studies demonstrating anti-inflammatory effects for C3a in the immune response. It is our hope that this review illuminates these apparently contradictory roles for C3a and challenges the general dogma surrounding C3a, which, historically, has ubiquitously been described as a proinflammatory mediator. In light of this, we urge investigators to use "inflammatory modulator" as the descriptor for C3a.
authors.affiliation: School of Biomedical Sciences, University of Queensland, St. Lucia 4072, Queensland, Australia.
authors.forename: Liam G
authors.initials: LG
authors.lastname: Coulthard
authors.affiliation: School of Biomedical Sciences, University of Queensland, St. Lucia 4072, Queensland, Australia t.woodruff@uq.edu.au.
authors.forename: Trent M
authors.identifier: http://orcid.org/0000-0003-1382-911X
authors.initials: TM
authors.lastname: Woodruff
mesh_terms: D000818:Animals; D003176:Complement C3 / Q000235:genetics / Q000276:immunology*; D015926:Complement C3a / Q000235:genetics / Q000276:immunology*; D015936:Complement C5a / Q000235:genetics / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D018836:Inflammation Mediators / Q000276:immunology*; D020556:Neutrophil Infiltration / Q000235:genetics / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology
chemical_list: C038245:C3 protein, human; D003176:Complement C3; D018836:Inflammation Mediators; D015926:Complement C3a; D015936:Complement C5a