Phagocytosis and phagosomal fate of surface-modified microparticles in dendritic cells and macrophages.
OBJECTIVE
We compared cationic, polyamine-coated microparticles (MPs) and anionic, protein-coated MPs with respect to their phagocytosis and phagosomal fate in dendritic cells (DCs) and macrophages (Mphi).


METHODS
Polystyrene MPs were surface modified by covalent coupling with fluorescein isothiocyanate-labeled polyamines or proteins. Phagocytosis of MP and the pH of their intracellular microenvironment was assessed in human-derived DCs and Mphi in a fluorescence plate reader. Visualization of MP phagocytosis in DCs was performed by transmission electron microscopy.


RESULTS
Phagocytosis of bovine serum albumin-coated MPs was low with significant differences between DC and Mphi, whereas phagocytosis of IgG-coated MPs was significantly enhanced in both cell types. Phagocytosis of both particle types resulted in an acidified phagosomal microenvironment (pH 4.6-5.1). In contrast, cationic, polyamine-coated MPs were equally phagocytosed by DCs and Mphi to a high extent and showed lower degrees of acidification (pH 6.0-6.8) in the phagosomal microenvironment. Transmission electron microscopy examination demonstrated all phagocytosed particles to be surrounded by a phagosomal membrane, which was more tightly apposed to the surface of cationic MPs and more loosely to bovine serum albumin-coated MPs.


CONCLUSIONS
Phagocytosis of cationic, polyamine-coated MPs is suggested to lead to diminished phagosomal acidification. Thus, cationic MP are potential carriers that may display beneficial features for the intracellular delivery of immunomodulating therapeutics and their protection against lysosomal degradation.
Thiele
Lars
L
Department of Applied BioSciences, Swiss Federal Institute of Technology Zurich (ETH), Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
Merkle
Hans P
HP
Walter
Elke
E
D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism*; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D008863:Microspheres; D010587:Phagocytosis / Q000502:physiology*; D010588:Phagosomes / Q000378:metabolism*; D013499:Surface Properties
D004337:Drug Carriers