THP-1 cells form foam cells in response to coculture with lipoproteins but not platelets.
The human monocytic leukemia cell line, THP-1, shares many properties with human monocyte-derived macrophages and might be a useful model for studying foam cell formation in vitro. Therefore, we examined the ability of THP-1 cells to accumulate cholesteryl esters, the hallmark feature of foam cells, in response to culture with native low density lipoprotein (LDL), modified LDL, and platelets. THP-1 cells stored more cholesteryl esters than macrophages in response to 200 micrograms/ml of LDL. Down-regulation of LDL receptors occurred in macrophages at lower LDL concentrations than in THP-1 cells. Phorbol ester-treated THP-1 cells stored more cholesteryl esters than human macrophages in response to 25-200 micrograms/ml of acetylated LDL. Because we have previously demonstrated that activated platelets enhanced macrophage cholesteryl ester storage, we examined the ability of THP-1 cells to store cholesteryl esters in response to coculture with platelets. Compared with macrophages, dividing THP-1 cells and phorbol ester-treated THP-1 cells accumulated only 50% and 33% as much cholesteryl esters, respectively. Furthermore, although platelets induced a 90% reduction in cholesterol synthesis in macrophages by day 5, cholesterol synthesis in THP-1 cells and phorbol ester-treated THP-1 cells was inhibited less than 50% by platelets. Nevertheless, both THP-1 cells and macrophages responded to platelets by increasing their secretion of apolipoprotein E. Therefore, we conclude that dividing THP-1 cells and phorbol ester-treated THP-1 cells are capable of forming foam cells in response to physiologic doses of both LDL and acetylated LDL, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Banka
C L
CL
Department of Immunology, Research Institute of Scripps Clinic, La Jolla, CA 92037.
Black
A S
AS
Dyer
C A
CA
Curtiss
L K
LK
D001057:Apolipoproteins E / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism*; D002784:Cholesterol / Q000096:biosynthesis; D002788:Cholesterol Esters / Q000378:metabolism; D004951:Esterification; D005487:Foam Cells / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000378:metabolism*; D011973:Receptors, LDL / Q000378:metabolism; D014407:Tumor Cells, Cultured
D001057:Apolipoproteins E; D002788:Cholesterol Esters; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D002784:Cholesterol