Uptake of oxidized low-density lipoprotein in a THP-1 cell line lacking scavenger receptor A

We previously isolated THP-1 subtype cells (sTHP-1), a cell line that expre sses scanty amounts of scavenger receptor A (ScR-A) and does not undergo fo am cell formation when incubated with acetylated low-density lipoprotein (A c-LDL). In this study, we investigated the accumulation of esterified chole sterol in sTHP-1 cells incubated with oxidized LDL (Ox-LDL), a physiologica lly modified lipoprotein in human. While sTHP-1 cells incubated with Ac-LDL accumulated only small amounts of esterified cholesterol, those incubated with Ox-LDL accumulated amounts similar to those accumulated by parent THP- 1 (pTHP-1) cells. sTHP-1 cells expressed CD36 in amounts similar to the amo unts expressed by pTHP-1 cells, and Ox-LDL was internalized through this CD 36. The amount of accumulated esterified cholesterol was 73-81% of that acc umulated in pTHP-1 cells expressing ScR-A. The levels of I-125-Ox-LDL bindi ng, association, and degradation in sTHP-1 cells were 64-70% of the corresp onding levels in pTHP-1 cells. In our experiments utilizing ScR-A-deficient sTHP-1 cells and a specific antibody against human CD36, most of the Ox-LD L interacted with the CD36 receptor. In addition, a substantial amount of O x-LDL (28-42%) was bound and degraded by sTHP-1 macrophages when both of th e two major scavenger receptors, ScR-A and CD36, were deficient or blocked. These results indicate that CD36 in macrophages plays an important role in foam cell formation by Ox-LDL, while additional scavenger receptor(s) may take part in significant pathways of Ox-LDL uptake in macrophages. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.