Non-conventional modification of low density lipoproteins: chemical models for macrophage recognition of oxidized LDL.
To define the structural and chemical criteria governing recognition of oxidized LDL (oxLDL) by mouse peritoneal macrophages (MPM), we exposed LDL to novel chemical modification agents that induce defined neutralizing and non-neutralizing alterations of lysine as models for distinct apoB adducts present in oxLDL. We found some exceptions to the usual notion that neutralization of lysine positive charges is the principal determinant governing MPM recognition. In addition, competitive binding experiments using chemically modified 125I-LDL preparations revealed that, whereas some modifications engendered recognition principally by the classical scavenger receptor class A (SRA), as seen for acetylated LDL (acLDL), chemical models of advanced aldehydic modifications of LDL led instead to MPM uptake mainly by oxLDL receptors distinct from SRA.
Hoppe
G
G
Department of Cell Biology, Cleveland Clinic Foundation, OH 44195, USA.
O'Neil
J
J
Sayre
L M
LM
Hoff
H F
HF
D000818:Animals; D002478:Cells, Cultured; D008054:Lipid Peroxides / Q000737:chemistry; D008077:Lipoproteins, LDL / Q000737:chemistry* / Q000378:metabolism; D008239:Lysine / Q000737:chemistry; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D010084:Oxidation-Reduction; D011971:Receptors, Immunologic / Q000378:metabolism*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B
D008054:Lipid Peroxides; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B; C099252:oxidized low density lipoprotein; D008239:Lysine