title: Mechanisms of fibrinogen domains: biomaterial interactions.
abstract: Spontaneous adsorption of fibrinogen is critical to the pathogenesis of biomaterial-mediated inflammatory responses. However, the mechanism by which adsorbed fibrinogen affects phagocyte responses is still not clear. To investigate the molecular interaction between fibrinogen and biomaterials, fibrinogen fragments (D100 and E50) were generated and used in the present study. The results indicate that biomaterial: D100 interaction is essential to fibrinogen-mediated inflammatory responses, because biomaterials precoated with D100, but not E50, prompt strong inflammatory responses. Furthermore, the results from in vitro studies show that whole molecule fibrinogen and D100 exhibit very similar protein:surface interactions. Specifically: (1) both D100 and fibrinogen have high affinity for biomaterial surfaces; and (2) the retention rates of adsorbed D100 in both in vivo and in vitro environments are as high as that for adsorbed fibrinogen. On the other hand, E50 does bind to biomaterials but with low affinity because, once bound, it is not tightly adherent to the biomaterial surfaces. Taken together, the results suggest that the mechanism of fibrinogen-mediated inflammatory responses may involve the following three consecutive events: (1) after contact with blood or tissue fluid, the D domain tends to interact with biomaterial surfaces and is important in the tight binding of fibrinogen to implant surfaces; (2) the biomaterial surface then promotes conformational changes within the D domain, exposing P1 epitope (gamma 190-202, which interacts with phagocyte Mac-1 integrin); and (3) the engagement of Mac-1 integrin with P1 epitope then triggers subsequent phagocyte adherence and reactions.
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: L
authors.initials: L
authors.lastname: Tang
mesh_terms: D000327:Adsorption; D000418:Albumins / Q000276:immunology / Q000502:physiology; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D004950:Esterases / Q000032:analysis; D005340:Fibrinogen / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000209:etiology* / Q000276:immunology; D008297:Male; D051379:Mice; D009195:Peroxidase / Q000032:analysis; D010586:Phagocytes / Q000276:immunology; D011093:Polyethylene Terephthalates / Q000009:adverse effects / Q000737:chemistry; D019736:Prostheses and Implants / Q000009:adverse effects; D011487:Protein Conformation; D013499:Surface Properties
chemical_list: D000418:Albumins; D001672:Biocompatible Materials; D011093:Polyethylene Terephthalates; C025539:Lavsan; D005340:Fibrinogen; D009195:Peroxidase; D004950:Esterases