title: Binding of a model regulator of complement activation (RCA) to a biomaterial surface: surface-bound factor H inhibits complement activation.
abstract: The complement system is an important inflammatory mediator during procedures such as cardiopulmonary bypass and hemodialysis when blood is exposed to large areas of biomaterial surface. This contact between blood and the biomaterials of implants and extracorporeal circuits leads to an inflammatory response mediated by the complement system. The aim of this study was to assess the ability of a complement regulator (factor H) immobilised on a biomaterial surface to inhibit complement cascade mediated inflammatory responses. The cross-linker N-succinimidyl 3-(2-pyridyldithio) propionate was used to immobilise factor H on a model biomaterial surface without affecting the biological activity of the inhibitor. Binding of factor H was then characterised using quartz crystal microbalance-dissipation (QCM-D) and enzyme immunoassays for products of complement activation: bound C3 fragments and soluble C3a, sC5b-9, and C1s-C1INA. Immobilised factor H reduced the amount C3 fragments deposited on the biomaterial surface after incubation with serum, plasma. or whole blood. In addition, lower levels of soluble C3a and sC5b-9 were generated after incubation with whole blood. In summary, we have demonstrated that complement activation on a highly activating model surface can be inhibited by immobilised factor H and have defined prerequisites for the preparation of future biomaterial surfaces with immobilised regulators of complement activation.
authors.affiliation: Section of Clinical Immunology, University Hospital, Uppsala, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Andersson
authors.forename: R
authors.initials: R
authors.lastname: Larsson
authors.forename: R
authors.initials: R
authors.lastname: Richter
authors.forename: K N
authors.initials: KN
authors.lastname: Ekdahl
authors.forename: B
authors.initials: B
authors.lastname: Nilsson
mesh_terms: D001672:Biocompatible Materials; D003167:Complement Activation; D003176:Complement C3 / Q000378:metabolism; D017242:Complement Factor H / Q000378:metabolism*; D003432:Cross-Linking Reagents; D006801:Humans; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000378:metabolism; D008422:Materials Testing; D008954:Models, Biological; D011485:Protein Binding; D013388:Succinimides; D013499:Surface Properties
chemical_list: D001672:Biocompatible Materials; C493495:CFH protein, human; D003176:Complement C3; D003432:Cross-Linking Reagents; D018836:Inflammation Mediators; D013388:Succinimides; C018151:N-succinimidyl 3-(2-pyridyldithio)propionate; D017242:Complement Factor H