title: Complement activation and inflammation triggered by model biomaterial surfaces.
abstract: Biomaterial-mediated complement activation repeatedly has been invoked as a trigger of phagocyte reactions and inflammation. However, a direct correlation between complement activation and inflammatory responses to biomaterial surfaces has yet to be established. Using an animal implantation model and gold surfaces bearing various thiol-linked functionalities, we investigated the potency of different surface groups in prompting complement activation in vitro and surface-mediated accumulation of inflammatory cells in vivo. Among the surfaces tested, mercaptoglycerol- and mercaptoethanol-bearing surfaces engendered the strongest inflammatory responses, as reflected by the accumulation of large numbers of adherent neutrophils and monocytes/macrophages. In contrast, L-cysteine-coated surfaces caused only minor inflammatory responses, and both glutathione-modified and untreated gold implants attracted minimal numbers of inflammatory cells. The accumulation of inflammatory cells on mercaptoglycerol surfaces appears to arise from surface-mediated complement activation because complement-depleted animals failed to exhibit inflammatory responses to mercaptoglycerol-modified implants. Furthermore, there is a close relationship between surface-mediated complement activation (as measured by in vitro iC3b/C5b-9 generation and C3 deposition) and in vivo inflammatory responses. At least in this animal model and with these model surfaces, our results indicate that surface-mediated complement activation can be responsible for the subsequent accumulation of inflammatory cells on implant surfaces.
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030-3498, USA.
authors.forename: L
authors.initials: L
authors.lastname: Tang
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.forename: H B
authors.initials: HB
authors.lastname: Elwing
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology / Q000633:toxicity*; D003167:Complement Activation / Q000187:drug effects*; D003170:Complement Pathway, Alternative / Q000187:drug effects; D003545:Cysteine / Q000494:pharmacology / Q000633:toxicity; D004546:Elapid Venoms / Q000494:pharmacology; D005549:Foreign-Body Reaction / Q000209:etiology*; D005978:Glutathione / Q000494:pharmacology / Q000633:toxicity; D005990:Glycerol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D006046:Gold / Q000494:pharmacology / Q000633:toxicity; D007249:Inflammation / Q000139:chemically induced*; D008297:Male; D008422:Materials Testing; D008623:Mercaptoethanol / Q000494:pharmacology / Q000633:toxicity*; D051379:Mice; D010586:Phagocytes / Q000502:physiology; D019736:Prostheses and Implants / Q000009:adverse effects*
chemical_list: D001672:Biocompatible Materials; D004546:Elapid Venoms; C016310:cobra venom factor; D008623:Mercaptoethanol; D006046:Gold; C009465:thioglycerol; D005978:Glutathione; D003545:Cysteine; D005990:Glycerol