Interaction of immunoglobulin-coupled liposomes with rat liver macrophages in vitro.
The interaction between liposomes coated with covalently linked rabbit immunoglobulin (RbIg-liposomes), and rat liver macrophages (Kupffer cells) in monolayer culture was studied biochemically with radioactive tracers and morphologically by electron microscopy. The attachment of immunoglobulin (Ig) to liposomes caused a five-fold increase in liposome uptake by the Kupffer cells at 37 degrees C, in comparison with uncoated liposomes. The uptake was linear with time for at least 4 h and linear with liposome concentration up to a lipid concentration of 0.2 mM. At 4 degrees C uptake, probably representing cell surface-bound liposomes, was reduced to a level of approx. 20% of the 37 degrees C values. Involvement of the Fc receptor in the uptake process was indicated by the reduction of RbIg-liposome uptake by more than 75% as a result of preincubating the cells with heat-aggregated human or rabbit Ig at concentrations (less than 2 mg/ml) at which bovine serum albumin (BSA) had virtually no effect on uptake. At high concentrations (10-35 mg/ml), however, albumin also reduced liposome uptake significantly (20-30%), which suggests an interaction of the RbIg-liposomes with the Kupffer cells that is partially non-specific. RbIg-liposome uptake was dependent on the amount of RbIg coupled to the liposomes. Maximal uptake values were reached at about 200 micrograms RbIg/mumol liposomal lipid. Electron microscopic observations on cells incubated with horseradish peroxidase-containing RbIg-liposomes demonstrated massive accumulation of peroxidase reaction product in intracellular vacuoles, showing that the uptake observed by label association represents true internalization.
D000818:Animals; D002478:Cells, Cultured; D004705:Endocytosis / Q000187:drug effects; D005260:Female; D006358:Hot Temperature; D007141:Immunoglobulin Fc Fragments / Q000276:immunology; D007136:Immunoglobulins; D007527:Isoenzymes / Q000032:analysis; D007728:Kupffer Cells / Q000276:immunology*; D008081:Liposomes; D008854:Microscopy, Electron; D010316:Particle Size; D009195:Peroxidase; D010544:Peroxidases / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D011961:Receptors, Fc / Q000276:immunology; D012710:Serum Albumin, Bovine / Q000494:pharmacology
D007141:Immunoglobulin Fc Fragments; D007136:Immunoglobulins; D007527:Isoenzymes; D008081:Liposomes; D011961:Receptors, Fc; D012710:Serum Albumin, Bovine; D010544:Peroxidases; D009195:Peroxidase