Implications of endogenous and exogenous lipoprotein lipase for the selective uptake of HDL3-associated cholesteryl esters by mouse peritoneal macrophages

Abstract

To investigate the implications of endogenous LPL on selective uptake of HDL3-associated cholesteryl esters (HDL3-CEs) by mouse peritoneal macrophages (MPMs), we have performed uptake experiments with MPMs obtained from control mice and transgenic knockout animals expressing LPL exclusively in muscle but not in macrophages. The capacity for HDL3 holoparticle, total HDL3-CE, and selective HDL3-CEs was independent of the expression of functional endogenous LPL (161 vs. 187, 1251 vs. 1300, and 1900 vs. 1113 ng HDL3/mg cell protein; control and LPL-deficient macrophages, respectively). Both control and LPL-deficient macrophages displayed, however, pronounced capacity for total HDL3-CE uptake in excess of HDL3 holoparticle uptake exceeding particle uptake by 7-fold. Despite the fact that endogenous LPL was without any effect on selective uptake, the addition of exogenous LPL led to a significant increase in cellular selective HDL3-CE uptake. Upon addition of purified LPL, HDL3 holoparticle (internalization and degradation), total HDL3-CE, and selective HDL3-CEs, was increased up to 2-fold. HDL3 holoparticle binding to control and LPL-deficient MPMs at 4 degrees C was enhanced 2.7- and 2.6-fold, respectively, in the presence of LPL. The present results suggest that endogenous LPL is without effect on selective uptake of HDL3-CEs. In contrast, the addition of exogenous LPL enhanced selective uptake of HDL3-CEs along with HDL3 holoparticle uptake apparently by the proposed bridging function of the enzyme.