Cells Involved in Removing Liposomes from the Blood Circulation: Why Are They So Special?

Abstract

In this contribution we describe and discuss (mostly published) experiments providing evidence favoring a decisive role of opsonizing plasma proteins in the removal of liposomes from the vascular compartment. Our conclusion is that cells will only bind and take up liposomes if they are anatomically accessible for the liposomes and if, in addition, they possess (specific) receptors for one or more proteins adsorbing to the liposomal surface. The relative contribution of each cell type fulfilling these criteria to over-all liposome clearance is dictated by the total number of cells in that population, the density of the receptor(s) involved, the affinity of those receptors for their respective ligands and the localization in the vascular system. It is concluded that only a few cell populations meet the criteria. Most are excluded because of inaccessibility while of the accessible ones several lack the proper opsonin receptors for significant liposome uptake. The significance of localization in the vasculature is illustrated by the hepatocytes whose accessibility is limited by the fenestrations in the endothelial lining of the liver sinusoids. The opsonin concept is extrapolated to cells other than macrophages; for example, the existence of hepatocyte-specific opsonins is proposed in order to explain the efficient uptake of small liposomes by this cell population. Because of their virtually complete lack of participation in plasma elimination of liposomes, some readily accessible cell types, such as the circulating blood cells and the vascular endothelial cells, are proposed to lack appropriate receptors. According to the views developed in this contribution the specialty of cells involved in liposome clearance therefore lies in the condition that they possess one or more receptors for plasma-derived proteins that spontaneously adsorb to the liposomal surface. One possible exception to the opsonin-determined concept is the fate of phosphatidylserine-containing liposomes. These may be cleared without or even in spite of involvement of opsonins, by virtue of a PS-specific receptor on macrophages.