title: Neutrophil adhesion on polyurethanes preadsorbed with high molecular weight kininogen.
abstract: Interaction of biomaterials with blood components including neutrophils is responsible for some of the clinical complications that have occurred in cardiopulmonary bypass, hemodialysis, and ventricular assist procedures. The possibility of inhibiting the initial adhesion of neutrophils to biomaterials has been studied extensively, but the problem remains unsolved. In this study, we investigated the effect of HK adsorption on polyurethane, a widely used component of extracorporeal and intracorporeal devices. HK and HKa were allowed to adsorb on 4 different charged polyurethanes: noncharged (PU), cationic (NR(4)), anionic (SO(3)), and zwitterionic (GPC) polyurethanes. The effect of kininogen adsorption on neutrophil adhesion, the surface density of the adsorbed kininogen, and the exposure of HK domains 3 and 5 (D(3) and D(5H)), which are responsible for the binding of HK to the neutrophil integrin alpha(m)beta(2) or Mac-1, were examined. On PU, NR(4), and SO(3), kininogen adsorption reached 80% of monolayer coverage when 100 pmol/mL or higher concentration of protein solutions were used. The NR(4) surface adsorbed the most kininogen along with a high exposure of D(3) and D(5H). The availability of D(3) and D(5H) allowed neutrophils to bind to the surface via the Mac-1 receptor; thus, on the NR(4) surface, adsorbed kininogens lost their antiadhesive property, which resulted in a high degree of neutrophil adhesion. Increasing Mac-1 expression by exposure to fMLP increased the neutrophil adhesion on this surface. In contrast, exposure of D(3) and D(5H) on SO(3) was significantly less, because HK binds to anionic surfaces with similar protein sequences used for cell binding. This low binding site exposure preserved the antiadhesive property of HK. GPC was resistant to neutrophil adhesion even in the absence of adsorbed kininogens because of its phosphorylcholine moiety. Thus, both SO(3) coupled with kininogen (or kininogen peptides) and GPC have the potential to markedly reduce neutrophil adhesion to biomaterial devices.
authors.affiliation: Department of Chemical Engineering, University of Delaware, Newark, DE, USA.
authors.forename: L Y
authors.initials: LY
authors.lastname: Yung
authors.forename: R W
authors.initials: RW
authors.lastname: Colman
authors.forename: S L
authors.initials: SL
authors.lastname: Cooper
mesh_terms: D000327:Adsorption; D000838:Anions; D000911:Antibodies, Monoclonal / Q000276:immunology; D002412:Cations; D002448:Cell Adhesion / Q000187:drug effects; D020099:Coated Materials, Biocompatible; D004797:Enzyme-Linked Immunosorbent Assay; D005112:Extracorporeal Circulation / Q000295:instrumentation; D006801:Humans; D007704:Kininogens / Q000737:chemistry / Q000494:pharmacology*; D008970:Molecular Weight; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects*; D011140:Polyurethanes; D017434:Protein Structure, Tertiary; D055672:Static Electricity
chemical_list: D000838:Anions; D000911:Antibodies, Monoclonal; D002412:Cations; D020099:Coated Materials, Biocompatible; D007704:Kininogens; D011140:Polyurethanes