title: Human complement Factor H modulates C1q-mediated phagocytosis of apoptotic cells.
abstract: Complement is implicated in the clearance of apoptotic cells by phagocytes. Deficiencies in early complement components, particularly C1q, are associated with an increased risk of the development of systemic lupus erythematosus. C1q is considered to be important in this process through interaction with apoptotic cells and phagocytes. In the present study, we confirm that apoptotic cells are recognized not only by C1q but also by the complement regulatory protein Factor H. Both C1q and Factor H bind to apoptotic cells in a dose-dependent and saturable manner. We further examined the role of C1q and Factor H in the clearance of apoptotic cells by monocytes. C1q enhanced uptake/adhesion of apoptotic cells by monocytes whereas Factor H alone had no effect on this process. However, when both C1q and Factor H were present on the apoptotic cell surface, C1q-mediated enhancement of uptake/adhesion of the apoptotic cells by monocytes was reduced. This effect of Factor H also occurred if monocytes were pre-treated with Factor H, and then exposed to C1q-coated apoptotic cells. The results were consistent with Factor H interacting with monocytes through the integrin CD11b/CD18. We conclude that under physiological conditions, Factor H may be important in controlling the inflammation which might arise from C1q deposition on apoptotic cells.
authors.affiliation: MRC Immunochemistry Unit, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
authors.forename: Yu-Hoi
authors.initials: YH
authors.lastname: Kang
authors.forename: Britta C
authors.initials: BC
authors.lastname: Urban
authors.forename: Robert B
authors.initials: RB
authors.lastname: Sim
authors.forename: Uday
authors.initials: U
authors.lastname: Kishore
mesh_terms: D017209:Apoptosis / Q000276:immunology; D039481:CD11b Antigen / Q000378:metabolism; D018821:CD18 Antigens / Q000378:metabolism; D018920:Coculture Techniques; D015922:Complement C1q / Q000172:deficiency / Q000276:immunology / Q000378:metabolism*; D017242:Complement Factor H / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D056747:Immunomodulation; D019169:Jurkat Cells; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D010587:Phagocytosis / Q000235:genetics / Q000276:immunology
chemical_list: D039481:CD11b Antigen; D018821:CD18 Antigens; D015922:Complement C1q; D017242:Complement Factor H