Acetylated low density lipoprotein inhibits the incorporation of arachidonic acid in phospholipids with a concomitant increase of cholesterol arachidonate in rat peritoneal macrophages.
The aim of our work was to evaluate the influence of native low density lipoproteins (LDL) and LDL chemically modified by acetylation (acLDL) on incorporation and release of arachidonic acid (AA) in rat peritoneal macrophages. Compared to a control group without treatment, 100 micrograms/ml of acLDL for 15 h considerably increased the incorporation of [3H]AA in cholesterol-ester (CE) of rat peritoneal macrophages and induced a decrease of 3H-labeled membrane phospholipids (PL). No effect was shown with LDL treatment. In the presence of acLDL, LS3251 (100 nM), an acyl-coenzyme A:cholesterol acyltransferase (ACAT) inhibitor, inhibited the [3H]AA incorporation into CE in macrophages. [3H]AA-prelabeled macrophages cultured for 15 h with acLDL (compared to macrophages untreated or treated with LDL) showed an increase of labeled CE and a decrease of labeled PL and of cyclooxygenase and lipoxygenase eicosanoid production. After zymosan stimulation of macrophages prelabeled with [3H]AA and treated with or without LDL or acLDL, AA release and eicosanoid production increased in all groups of macrophages. The inhibition of eicosanoid production in foam cells does not seem to be linked to an inhibition of phospholipase but rather paralleled to an increase of the cholesterol [3H]arachidonate. A significant portion of cellular arachidonate released from phospholipids, in particular from phosphatidylcholine, could serve as a substrate to ACAT in this foam cell.
Laboratoire de la Signalisation et de la Différenciation des Macrophages, INSERM CJF91-07, Toulouse, France.
C
C
Pollaud
S
S
Krause
J C
JC
Lepert
C
C
Orfila
M
M
Séguélas
D
D
Festal
J
J
Decerprit
B
B
Pipy
D000107:Acetylation; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D001095:Arachidonic Acids; D002788:Cholesterol Esters / Q000378:metabolism*; D015777:Eicosanoids / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008084:Lipoxygenase / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D010743:Phospholipids / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors
D001095:Arachidonic Acids; D002788:Cholesterol Esters; D015777:Eicosanoids; D004791:Enzyme Inhibitors; D008077:Lipoproteins, LDL; D010743:Phospholipids; C032629:acetyl-LDL; D016718:Arachidonic Acid; C029382:cholesteryl arachidonate; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D002785:Sterol O-Acyltransferase