MINIMALLY OXIDIZED LOW-DENSITY-LIPOPROTEIN INCREASES EXPRESSION OF SCAVENGER RECEPTOR-A, CD36, AND MACROSIALIN IN RESIDENT MOUSE PERITONEAL-MACROPHAGES

Fully oxidized LDL (OxLDL) is believed to contribute to atherogenesis in part by virtue of uptake into macrophages via specific scavenger re ceptors. This phenomenon results in the formation of cholesterol-loade d foam cells, a major component of atherosclerotic lesions, The presen t study is directed at examining the effects of OxLDL and minimally ox idized LDL (MM-LDL) on scavenger receptor expression and activity in m ouse peritoneal resident macrophages. Macrophages were preincubated wi th MM-LDL or OxLDL at concentrations of 25 or 50 mu g/mL for 24 to 48 hours, after which their ability to bind and take up I-125-OxLDL or I- 125-acetylated LDL (AcLDL) was determined. MM-LDL pretreatment induced a clear increase of cell association and degradation of I-125-OxLDL a nd I-125-AcLDL. Pretreatment with OxLDL also enhanced scavenger recept or activity, but to a lesser degree. Neither native LDL nor AcLDL had any effect. Scatchard analysis showed that preincubation with 50 mu g/ mL MM-LDL for 48 hours increased the B-max of I-125-OxLDL and I-125-Ac LDL by 139% and 154%, respectively, without significantly changing the ir affinity. Lipids extracted from MM-LDL also significantly induced s cavenger receptor activity, but to a lesser extent than did intact MM- LDL. MM-LDL pretreatment increased both mRNA levels and protein levels of scavenger receptor A, CD36, and macrosialin. On the other hand, Ox LDL pretreatment increased expression of macrosialin only. These resul ts, showing that MM-LDL can upregulate scavenger receptor expression i n mouse resident peritoneal macrophages, suggest that clearance of OxL DL by macrophages in lesions is more effective, in part because the Ox LDL precursor, MM-LDL, primes the macrophage for foam cell generation.