title: Factor H as a regulator of the classical pathway activation.
abstract: C1q, the first subcomponent of the classical pathway, is a charge pattern recognition molecule that binds a diverse range of self, non-self and altered self ligands, leading to pro-inflammatory complement activation. Although complement is required for tissue homeostasis as well as defence against pathogens, exaggerated complement activation can be damaging to the tissue. Therefore, a fine balance between complement activation and inhibition is necessary. We have recently found that factor H, a polyanion recognition molecule and soluble regulator of alternative pathway activation in blood and on cell surfaces, can directly compete with C1q in binding to anionic phospholipids (cardiolipin), lipid A and Escherichia coli (three known activators of the classical pathway) and acts as a direct down regulator of the complement classical pathway. This ability of factor H to dampen classical pathway activation is distinct from its role as an alternative pathway down-regulator. Thus, by directly competing for specific C1q ligands (exogenous as well as endogenous), factor H is likely to be involved in fine-tuning and balancing the C1q-driven inflammatory processes in autoimmunity and infection. However, in the case of apoptotic cells, C1q-mediated enhancement of uptake/adhesion of the apoptotic cells by monocytes was reduced by factor H. Thus, factor H may be important in controlling the inflammation, which might arise from C1q deposition on apoptotic cells.
authors.affiliation: Centre for Infection, Immunity and Disease Mechanisms, Biosciences, School of Health Sciences and Social Care, Brunel University, Uxbridge, London, UK. uday.kishore@brunel.ac.uk
authors.forename: Uday
authors.initials: U
authors.lastname: Kishore
authors.forename: Robert B
authors.initials: RB
authors.lastname: Sim
mesh_terms: D017209:Apoptosis / Q000276:immunology; D002308:Cardiolipins / Q000276:immunology / Q000378:metabolism; D015922:Complement C1q / Q000276:immunology* / Q000378:metabolism; D017242:Complement Factor H / Q000276:immunology* / Q000378:metabolism; D003171:Complement Pathway, Classical / Q000276:immunology*; D004926:Escherichia coli / Q000276:immunology / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D008050:Lipid A / Q000276:immunology / Q000378:metabolism
chemical_list: D002308:Cardiolipins; D018836:Inflammation Mediators; D008050:Lipid A; D015922:Complement C1q; D017242:Complement Factor H