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Quantitative Analysis Of Liposome-cell Interactions In Vitro: Rate Constants Of Binding And Endocytosis With Suspension And Adherent J774 Cells And Human Monocytes.
K. Lee, S. Nir, D. Papahadjopoulos
Published 1993 · Biology, Medicine
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We have characterized the parameters describing the total association (uptake) of liposomes with murine macrophage-like cell line J774 cells and human peripheral blood monocytes at 4 degrees C and at 37 degrees C with or without inhibitors of endocytosis. The uptake of neutral liposomes composed of phosphatidylcholine (PC)/cholesterol (Chol) (2:1 mole ratio) is about 10-fold lower than that of negatively charged liposomes composed of phosphatidylserine (PS)/PC/Chol (1:1:1). However, the rate of uptake of PC/Chol liposomes at 37 degrees C is still 10-fold higher than that by fluid-phase pinocytosis. The uptake of liposomes, which is mediated by high-affinity binding to the cell surface binding sites and subsequent endocytosis, could be simulated and predicted by model calculations employing mass action kinetics. The number of binding sites, affinity constants of binding at 37 degrees C and 4 degrees C, on- and off-rate constants of binding, and endocytic rate constants for both types of liposomes were determined. The number of binding sites and the binding constants for PS/PC/Chol liposomes binding to J774 cells is severalfold to an order of magnitude higher than that for PC/Chol liposomes, but the rate constants at which they are endocytosed following binding to the cells are similar for both liposome types. The binding of liposomes, especially PS/PC/Chol, to J774 cells and monocytes is greatly enhanced by adherence of cells to plastic substratum and is also increased by maturation/differentiation in the case of monocytes. Our quantitative analysis indicates that the binding and endocytosis of liposomes, especially PS-containing liposomes, is mediated by binding sites that have strong affinity, comparable to or about an order of magnitude smaller than other known particle-cell interactions with specific receptors such as virus and lipoproteins binding to cells.
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