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 expresses scanty amounts of scavenger receptor A (ScR-A) and does not undergo foam cell formation when incubated with acetylated low-density lipoprotein (Ac-LDL). In this study, we investigated the accumulation of esterified cholesterol in sTHP-1 cells incubated with oxidized LDL (Ox-LDL), a physiologically 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 amounts expressed by pTHP-1 cells, and Ox-LDL was internalized through this CD36. The amount of accumulated esterified cholesterol was 73-81% of that accumulated in pTHP-1 cells expressing ScR-A. The levels of 125I-Ox-LDL binding, association, and degradation in sTHP-1 cells were 64-70% of the corresponding 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-LDL interacted with the CD36 receptor. In addition, a substantial amount of Ox-LDL (28-42%) was bound and degraded by sTHP-1 macrophages when both of the 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.
Sugano
R
R
Department of Etiology and Pathophysiology, National Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan.
Yamamura
T
T
Harada-Shiba
M
M
Miyake
Y
Y
Yamamoto
A
A
D015152:Blotting, Northern; D018955:CD36 Antigens / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism*; D051117:Scavenger Receptors, Class A; D014407:Tumor Cells, Cultured
D018955:CD36 Antigens; D002788:Cholesterol Esters; D008077:Lipoproteins, LDL; D051117:Scavenger Receptors, Class A; C032629:acetyl-LDL; C099252:oxidized low density lipoprotein