Receptor-mediated endocytosis of poly(acrylic acid)-conjugated liposomes by macrophages.
The uptake characteristics of negatively-charged liposomes made by conjugation of poly(acrylic acid) (PAA) were studied with respect to cultured RAW macrophages. The PAA-conjugated liposomes were internalized and digested in an acidic compartment at a much faster rate than the unmodified phosphatidylcholine (PC) liposomes. After incubation for 18 h, an over 5-fold increase in the uptake of PC liposomes was obtained by PAA conjugation. Subsequently, part of the aqueous phase of the internalized liposomes was exocytosed. Recognition of PAA by the macrophages seems to be responsible for the enhanced uptake of PAA-conjugated liposomes. Cross-competition experiments showed that PAA-conjugated liposomes inhibited the uptake of acetylated-low density lipoprotein (acetyl-LDL) by the macrophages and vice versa. The uptake of PAA-conjugated liposomes was also inhibited by dextran sulfate and maleylated-bovine serum albumin (maleyl-BSA), which are also known to bind to scavenger receptors. Poly(C) and BSA, which are not ligands for the scavenger receptor, competed poorly with the uptake of PAA-conjugated liposomes. Enhanced uptake of PAA-conjugated liposomes by CHO cells with low scavenger receptor expression was not observed. Unexpectedly, LDL, which is not a ligand for scavenger receptor, also partially inhibited the uptake of PAA-conjugated liposomes. The interaction of PAA-conjugated liposomes with macrophages is complex, and the endocytosis of PAA-conjugated liposomes most likely involves multiple receptors and/or pathways. The data obtained suggest that the high affinity binding of PAA-conjugated liposomes to macrophages may be due to recognition of the negative charges of PAA by cell surface receptors, including the scavenger receptor.
Fujiwara
M
M
Division of Chemistry and Chemical Engineering, California Institute of Technology (Caltech 127-72), Pasadena 91125, USA.
Baldeschwieler
J D
JD
Grubbs
R H
RH
D000180:Acrylic Resins / Q000378:metabolism*; D000418:Albumins / Q000494:pharmacology; D000818:Animals; D001190:Arylsulfonates / Q000378:metabolism; D001667:Binding, Competitive; D016466:CHO Cells; D002478:Cells, Cultured; D002784:Cholesterol / Q000031:analogs & derivatives / Q000378:metabolism; D006224:Cricetinae; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism; D005089:Exocytosis; D005456:Fluorescent Dyes / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology; D007444:Inulin / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D011066:Poly C / Q000494:pharmacology; D012710:Serum Albumin, Bovine; D013696:Temperature
D000180:Acrylic Resins; D000418:Albumins; D001190:Arylsulfonates; D005456:Fluorescent Dyes; D008077:Lipoproteins, LDL; D008081:Liposomes; C049877:maleylalbumin; D012710:Serum Albumin, Bovine; D011066:Poly C; C006903:carbopol 940; D006493:Heparin; D007444:Inulin; D002784:Cholesterol; C005047:pyranine