Blood, Vol. 94 No. 8 (October 15), 1999:
pp. 2716-2724
Neutrophil Adhesion on Polyurethanes Preadsorbed With High Molecular
Weight Kininogen
Lin-Yue L. Yung,
Robert W. Colman, and
Stuart L. Cooper
From the Department of Chemical Engineering, University of Delaware,
Newark, DE; and the Sol Sherry Thrombosis Research Center, Temple
University School of Medicine, Philadelphia, PA.
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
(NR4), anionic (SO3), 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 (D3 and D5H),
which are responsible for the binding of HK to the neutrophil integrin
m
2 or Mac-1, were examined. On PU,
NR4, and SO3, kininogen adsorption reached 80%
of monolayer coverage when 100 pmol/mL or higher concentration of
protein solutions were used. The NR4 surface adsorbed the
most kininogen along with a high exposure of D3 and
D5H. The availability of D3 and D5H
allowed neutrophils to bind to the surface via the Mac-1 receptor;
thus, on the NR4 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
D3 and D5H on SO3 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 SO3 coupled
with kininogen (or kininogen peptides) and GPC have the potential to
markedly reduce neutrophil adhesion to biomaterial devices.
