NONCONVENTIONAL MODIFICATION OF LOW-DENSITY LIPOPROTEINS - CHEMICAL-MODELS FOR MACROPHAGE RECOGNITION OF OXIDIZED LDL

To define the structural and chemical criteria governing recognition o f oxidized LDL (oxLDL) by mouse peritoneal macrophages (MPM), we expos ed LDL to novel chemical modification agents that induce defined neutr alizing and non-neutralizing alterations of lysine as models for disti nct apoB adducts present in oxLDL. We found some exceptions to the usu al notion that neutralization of lysine positive charges is the princi pal determinant governing MPM recognition. In addition, competitive bi nding experiments using chemically modified I-125-LDL preparations rev ealed that, whereas some modifications engendered recognition principa lly by the classical scavenger receptor class A (SRA), as seen for ace tylated LDL (acLDL), chemical models of advanced aldehydic modificatio ns of LDL led instead to MPM uptake mainly by oxLDL receptors distinct from SRA. (C) 1997 Elsevier Science B.V.