title: Competitive adsorption of serum proteins at microparticles affects phagocytosis by dendritic cells.
abstract: Serum protein adsorption to the surface of particulate synthetic drug carrier systems has a major influence on their uptake by phagocytes. The influence of alpha2-human serum glycoprotein (alpha2GP) on the phagocytosis of various surface modified microparticles was studied in dendritic cells (DC) and was compared with a potent opsonin, IgG, and a dysopsonin, human serum albumin (HSA). The microparticles were administered to DC before and after the incubation with alpha2GP, IgG and HSA in single, binary or ternary protein systems and in whole blood serum. Phagocytosis of microparticles was vastly affected by the surface character of the microparticles themselves and by the adsorption of the proteins. Poly-L-lysine (PLL)-modified microparticles were under all conditions internalized with highest efficiency which is suggested to be mediated by their positive surface charge. The adsorption of commonly phagocytosis promoting proteins reduced the uptake of PLL-modified particles and is explained by compensation of the positive surface charge by the adsorbed negatively charged proteins. In all other particle types tested, freshly adsorbed alpha2GP was found to exhibit a strong phagocytosis promoting activity which was comparable to that of adsorbed IgG. Interestingly, this opsonic activity was lost already 2 h after adsorption to the particle surface. Protein adsorption from binary and ternary protein systems and from whole blood serum occurred in a competitive manner. Significant inhibition of phagocytosis was observed, even when HSA was combined with strong opsonins such as alpha2GP or IgG or in mixtures of all three proteins, indicating the importance of studying the influence of protein adsorption in protein mixtures.
authors.affiliation: Department of Applied BioSciences, Swiss Federal Institute of Technology (ETH), Winterthurerstrasse 190, Zurich 8057, Switzerland.
authors.forename: Lars
authors.initials: L
authors.lastname: Thiele
authors.forename: Julia E
authors.initials: JE
authors.lastname: Diederichs
authors.forename: Regina
authors.initials: R
authors.lastname: Reszka
authors.forename: Hans P
authors.initials: HP
authors.lastname: Merkle
authors.forename: Elke
authors.initials: E
authors.lastname: Walter
mesh_terms: D000327:Adsorption; D001667:Binding, Competitive; D001672:Biocompatible Materials; D001798:Blood Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000502:physiology*; D016503:Drug Delivery Systems; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D008422:Materials Testing; D008863:Microspheres; D010587:Phagocytosis; D011107:Polylysine; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism; D000511:alpha-Macroglobulins / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials; D001798:Blood Proteins; D007074:Immunoglobulin G; D012709:Serum Albumin; D000511:alpha-Macroglobulins; D011107:Polylysine