Macrophage colony-stimulating factor regulates both activities of neutral and acidic cholesteryl ester hydrolases in human monocyte-derived macrophages.
Macrophage colony-stimulating factor (M-CSF) regulates cholesterol metabolism in vivo and in vitro. We studied the effects of M-CSF on enzyme activities of acidic cholesteryl ester (CE) hydrolase, neutral CE hydrolase, and acyl-coenzyme A:cholesterol acyltransferase (ACAT), all of which are involved in cellular cholesterol metabolism in macrophages. During the differentiation of monocytes to macrophages, these enzyme activities were induced and further enhanced in response to M-CSF. M-CSF (100 ng/ml) enhanced acidic and neutral CE hydrolase and ACAT activities by 3.2-, 4-, and 2.3-fold, respectively, in the presence of acetyl LDL. The presence of acetyl LDL influenced these enzyme activities. ACAT and acidic CE hydrolase activities were increased and neutral CE hydrolase activity was decreased, indicating that these enzymes are regulated by intracellular cholesterol enrichment. M-CSF increased the ratios of acidic CE hydrolase to ACAT activity and of neutral CE hydrolase to ACAT activity. The results suggest that M-CSF enhances net hydrolysis of CE by stimulating the two CE hydrolases to a greater extent than ACAT, and M-CSF may reduce the rate of atherogenesis.
Inaba
T
T
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Shimano
H
H
Gotoda
T
T
Harada
K
K
Shimada
M
M
Kawamura
M
M
Yazaki
Y
Y
Yamada
N
N
D001483:Base Sequence; D003994:Bucladesine / Q000494:pharmacology; D002454:Cell Differentiation; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood; D000242:Cyclic AMP / Q000097:blood; D004790:Enzyme Induction; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis* / Q000097:blood; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000494:pharmacology; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology*; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D002787:Sterol Esterase / Q000096:biosynthesis* / Q000097:blood; D002785:Sterol O-Acyltransferase / Q000097:blood; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007527:Isoenzymes; D008077:Lipoproteins, LDL; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D011994:Recombinant Proteins; C032629:acetyl-LDL; D003994:Bucladesine; D016173:Macrophage Colony-Stimulating Factor; D002784:Cholesterol; D000242:Cyclic AMP; D002785:Sterol O-Acyltransferase; D002787:Sterol Esterase; D013755:Tetradecanoylphorbol Acetate