Enhanced macrophage uptake of elastase-modified high-density lipoproteins.
Incubation of human HDL (d = 1.063-1.21 g/ml) with monocyte-derived elastase causes selective proteolysis of apoA-II and apoA-I apolipoproteins. We have found that elastase-digested HDL (ED-HDL) bind to J774-A1 murine macrophages with enhanced affinity and are internalized and degraded at a rate threefold higher than that of native HDL. Unlike oxidized LDL and HDL and proteolytically modified LDL, the uptake of ED-HDL lipoproteins does not affect the cellular lipid biosynthesis nor modify the cell lipid content. The cell surface binding of (125)I-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-engorging macrophages is regarded as an important event during atherogenesis. By enhancing the cellular uptake of HDL this process can lead to a local decrease of antiatherogenic HDL particles.
Pirillo
A
A
Department of Pharmacology, Istituto di Scienze Farmacologiche, Milan, Italy.
Ghiselli
G
G
D000818:Animals; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007700:Kinetics; D019272:Leukocyte Elastase / Q000378:metabolism*; D050356:Lipid Metabolism; D008075:Lipoproteins, HDL / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism
D002788:Cholesterol Esters; D008075:Lipoproteins, HDL; D014280:Triglycerides; D002784:Cholesterol; D019272:Leukocyte Elastase