Binding and uptake of differently oxidized low density lipoprotein in mouse peritoneal macrophages and THP-1 macrophages: Involvement of negative charges as well as oxidation-specific epitopes

Oxidatively modified low-density lipoprotein (LDL) has been found in vivo, and oxidized LDL (oxLDL) could bind to scavenger receptors, leading to foam cell formation. Macrophages bear a number of different scavenger receptors for oxLDL, and macrophages of different origins may have a different scave nger receptor repertoire. In addition, LDL oxidized to different degrees ma y differ in the ability to bind macrophage scavenger receptors. In this stu dy, we characterized the patterns of the binding and uptake of differently oxidized LDL in mouse peritoneal macrophages (MPM) and human THP-1 macropha ges, and the influence of negative charge and oxidation-specific epitopes i n oxLDL on these processes. Thresholds of increased binding and uptake in M PM were found when LDL was oxidized to the degrees with a relative electrop horetic mobility (REM) of 2.6 (minor threshold) and 3.0 (major threshold), corresponding to 49 and 57%, respectively, of the loss of free amino groups in these oxLDL. There was no threshold for the binding of oxLDL to THP-1 m acrophages, while for uptake, a major threshold with REM of 3.0 (57% free a mino groups lost) was found. The presence of the F(ab')(2) fragments of the monoclonal antibody OB/04, which was raised against copper-oxidized LDL, l ed to the reduction of the binding and uptake, respectively, of Eu3+-oxLDL (REM:3.6) in MPM by 31 and 29%, and by 19 and 22% in THP-1 macrophages. It is concluded that LDL oxidized to different degrees binds differently to ma crophages, and the patterns of binding and uptake are different for MPM and human THP-1 macrophages. Both, the negative charge and the oxidation-speci fic epitopes of oxLDL are involved in these processes. J. Cell. Biochem. 81 :557-569, 2001. (C) 2001 Wiley-Liss, Inc.