Enhanced macrophage uptake of elastase-modified high-density lipoproteins

Incubation of human HDL (d = 1.063-1.21 g/ml) with monocyte-derived elastas e causes selective proteolysis of apoA-II and apoA-I apolipoproteins. me ha ve found that elastase-digested HDL (ED-HDL) bind to J774-Al murine macroph ages with enhanced affinity and are internalized and degraded at a rate thr eefold higher than that of native HDL. Unlike oxidized LDL and HDL and prot eolytically modified LDL, the uptake of ED-HDL lipoproteins does not affect the cellular Lipid biosynthesis nor modify the cell lipid content. The cel l surface binding of I-125-ED-HDL can be competed by native HDL but not by acetylated LDL, consistent with the idea that ED-HDL are recognized by the class B type I scavenger receptor. The liberation of elastase by lipid-engo rging macrophages is regarded as an important event during atherogenesis. B y enhancing the cellular uptake of HDL this process can lead to a local dec rease of antiatherogenic HDL particles. (C) 2000 Academic Press.