COMPLEMENT-DEPENDENT AND INDEPENDENT LIPOSOME UPTAKE BY PERITONEAL-MACROPHAGES - CHOLESTEROL CONTENT DEPENDENCY

The uptake mechanisms of liposomes by rat peritoneal macrophages (PMs) were investigated. Incubation of liposomes with fresh rat serum enhan ced the uptake of liposomes depending on the liposome size and cholest erol (CH) content. The binding of liposomes was also enhanced by serum , and this increase depended on the size and CH content as in the case of liposome uptake, which suggested that the binding of opsonized lip osomes with PMs govern the extent in liposome uptake. The rate constan t for the internalization (k(int)) was calculated by measuring both up take and binding. The k(int) cannot explain the variation of liposome uptake for different sizes and CH contents. The kint values for liposo mes with high (44%) and medium (33%) CH contents were constant (2.5 h( -1)), while those for liposomes with low (22%) CH content were signifi cantly elevated (5-9 h(-1)). These results indicate the presence of at least two kinds of uptake mechanisms of liposomes, Treatment of serum with anti-C3 antibody completely inhibited the enhanced uptake of CH- high, large liposomes, which suggested that complement receptor-mediat ed phagocytosis may be an uptake mechanism for CH-high and -medium lip osomes. In addition, complement-independent enhanced uptake was sugges ted for CH-low liposomes, since no inhibition was observed for CH-low liposomes by anti-C3 antibody and these liposomes were disintegrated i n serum via compliment-independent pathway. These results provided evi dence that PMs take up liposomes via complement-dependent and independ ent mechanisms depending on the CH content of the liposomes.