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 densit y lipoproteins (LDL) and LDL chemically modified by acetylation (acLDL ) on incorporation and release of arachidonic acid (AA) in rat periton eal macrophages. Compared to a control group without treatment, 100 mu g/ml of acLDL for 15 h considerably increased the incorporation of [H -3]AA in cholesterol-ester (CE) of rat peritoneal macrophages and indu ced a decrease of H-3-labeled membrane phoosholipids (PL). No effect w as shown with LDL treatment. In the presence of acLDL, LS3251 (100 nM) , an acyl-coenzyme A:cholesterol acyltransferase (ACAT) inhibitor, inh ibited the [H-3]AA incorporation into CE in macrophages. [H-3]AA-prela beled macrophages cultured for 15 h with acLDL (compared to macrophage s untreated or treated with LDL) showed an increase of labeled CE and a decrease of labeled PL and of cyclooxygenase and lipoxygenase eicosa noid production. After zymosan stimulation of macrophages prelabeled w ith [H-3]AA and treated with or without LDL or acLDL, AA release and e icosanoid production increased in all groups of macrophages. The inhib ition of eicosanoid production in foam cells does not seem to be linke d to an inhibition of phospholipase but rather paralleled to an increa se of the cholesterol [H-3]arachidonate. A significant portion of cell ular arachidonate released from phospholipids, in particular from phos phatidylcholine, could serve as a substrate to ACAT in this foam cell.