title: Molecular basis of biomaterial-mediated foreign body reactions.
abstract: Despite being inert and nontoxic, implanted biomaterials often trigger adverse foreign body reactions such as inflammation, fibrosis, infection, and thrombosis. With regard to the inflammatory responses to biomaterial implants, it was previously found that a crucial precedent event was the spontaneous adsorption and denaturation of fibrinogen on implant surfaces. It was further found that interactions between the phagocyte integrin Mac-1 (CD11b/CD18) and one short sequence within the fibrinogen D domain (gamma 190-202; P1) at least partially explained phagocyte accumulation on implant surfaces. However, the reason that adsorbed fibrinogen is proinflammatory--while soluble fibrinogen clearly is not--remained obscure. In this study, therefore, the question of how fibrinogen is converted to a proinflammatory state when adsorbed to biomaterial surfaces is investigated. In soluble fibrinogen, the 13 amino acid P1 sequence was found to be hidden. However, the adsorption and denaturation of fibrinogen on the surfaces of commonly used biomaterials lead to the exposure of P1 and a second neo-epitope, gamma 377-395 (P2), which also interacts with Mac-1 and is similarly occult in the soluble protein. The extent of biomaterial-mediated P1 and P2 exposure appears directly related to the severity of inflammatory responses to a test panel of biomaterials. Finally, thrombin-mediated conversion of fibrinogen to fibrin also exposes both P1 and P2 epitopes. These observations may help explain both the inflammation caused by many types of implanted biomaterials and that which occurs naturally following thrombotic events. (Blood. 2001;98:1231-1238)
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: W J
authors.initials: WJ
authors.lastname: Hu
authors.forename: J W
authors.initials: JW
authors.lastname: Eaton
authors.forename: T P
authors.initials: TP
authors.lastname: Ugarova
authors.forename: L
authors.initials: L
authors.lastname: Tang
mesh_terms: D000327:Adsorption; D000818:Animals; D001665:Binding Sites; D001672:Biocompatible Materials / Q000009:adverse effects* / Q000378:metabolism; D002448:Cell Adhesion; D000939:Epitopes; D005337:Fibrin / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D005549:Foreign-Body Reaction / Q000209:etiology*; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008297:Male; D051379:Mice; D023421:Models, Animal; D010586:Phagocytes / Q000737:chemistry / Q000502:physiology; D011093:Polyethylene Terephthalates / Q000009:adverse effects / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013917:Thrombin / Q000494:pharmacology
chemical_list: D001672:Biocompatible Materials; D000939:Epitopes; D016177:Macrophage-1 Antigen; D011093:Polyethylene Terephthalates; D005337:Fibrin; D005340:Fibrinogen; D013917:Thrombin