Adsorbed serum proteins responsible for surface dependent human macrophagebehavior

Substrate specific cellular responses are the result of a complex biologica l system that includes protein adsorption, receptor-ligand binding, and sig nal transduction. This investigation attempted to identify specific protein s adsorbed from human serum that may be responsible for the previously repo rted in vitro surface dependent behavior of human macrophages and foreign b ody giant cells (FBGCs). The adsorption of human albumin, alpha(2)-macroglo bulin, complement factor 3b, fibronectin, IgG, thrombospondin, vitronectin (VN), and von Willebrand factor (vWF) from a 25% serum solution was quantif ied with I-125-labeled protein. Adsorption substrates included clean glass, alkyl-silane modified glass, amino-silane modified glass, poly(ethylene ox ide) (PEO)-coupled glass, and the reference biomaterials poly(etherurethane urea), Silastic(R), and poly(tetrafluoroethylene) (PTFE). Following quanti fication of 2-h adsorption, surfaces were treated with sodium dodecyl sulfa te (SDS) and the level of adsorbed proteins remaining was quantified. The p re- and post-SDS adsorption were both compared to previously reported surfa ce dependent in vitro macrophage and FBGC behavior on the same surfaces; ho wever, as the percentage of initially adsorbed protein that remained adsorb ed after SDS treatment, correlated well with previously reported in vitro c ellular behavior indicating that adsorbed vWF, IgG, and VN may be involved in the modulation of adherent macrophage and FBGC behavior. Those surfaces that strongly adsorbed vWF also inhibited longterm macrophage adhesion, whi le those surfaces that strongly adsorbed IgG promoted long-term macrophage adhesion. In addition, the highest levels of FBGC formation had been observ ed only on those surfaces that strongly adsorbed VN. Subsequent human monoc yte cultures on protein preadsorbed substrates confirmed the inhibitory eff ect of adsorbed vWF and the promoting effect of IgG on longterm macrophage adhesion as predicted by adsorption strength correlations. However, preadso rbed VN was not observed to modulate FBGC formation, which is in contrast t o the conclusions of the adsorption correlations. (C) 2000 John Wiley & Son s, Inc.