Liposome uptake by human leukocytes. Enhancement of entry mediated by human serum and aggregated immunoglobulins.
The entry of immunoglobulin-coated liposomes into human leukocytes bearing Fc receptors was evaluated using two methods: (i) the cellular association of liposomal markers (3H-labelled phosphatidylcholine, lipid phase; [14C]inulin, aqueous phase), and (ii) the ultrastructural cytochemistry of cells following incubation of cells with liposomes containing a cytochemical marker (horseradish peroxidase) in the aqueous spaces. The entry of liposomes into a cell population composed predominantly of neutrophils was linear for 10--15 min and was mediated by an active process that appeared to be both energy- and surface-dependent. This uptake could be largely inhibited by incubation at 0 degrees C, and by exposure to glutaraldehyde, iodoacetamide, N-ethylmaleimide, and an excess of aggregated immunoglobulins. Entry into cells of multilamellar liposomes was saturable, displaying affinity constants of 1.1 and 1.7 mM. Ultrastructural analysis of the heterogeneous leukocyte population showed that monocytes took up liposomes more actively than neutrophils and lymphocytes. Moreover, liposomes were almost always found within the leukocytes, rather than adherent to the outer plasma membrane. The relative avidity of monocytes was confirmed by comparing the uptake of radiolabelled liposomes by a 'pure' neutrophil population, a 'mixed' neutrophil population, and a 'mononuclear cell' population. Precoating liposomes with high molecular weight aggregates of human immunoglobulin G resulted in enhanced serum-independent uptake. The fraction of aggregated immunoglobulin G which was most effective in provoking uptake of coated liposomes also stimulated the greatest amount of lysosomal enzyme secretion. These data suggest that the interaction (precoating) of liposomes with either high molecular weight aggregates of immunoglobulin G or with serum enhances their subsequent uptake by human leukocytes.
D001798:Blood Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D007962:Leukocytes / Q000378:metabolism* / Q000648:ultrastructure; D008081:Liposomes / Q000378:metabolism*; D013499:Surface Properties
D001798:Blood Proteins; D007074:Immunoglobulin G; D008081:Liposomes