Phosphatidylinositol turnover in human monocyte‐derived macrophages by native and acetyl LDL

Abstract

Monocyte‐derived macrophages play a key role in pathogenesis of atherosclerosis. However, the mechanism of activating macrophages in atheromatous lesions has not been fully investigated. This report describes the contribution of phosphatidylinositol turnover to the uptake of low density lipoproteins (LDL) by macrophages. Both native and acetyl LDL stimulated inositol 1,4,5‐triphosphate (IP₃) formation in a dose‐dependent manner at concentrations of 0–70 μg/ml. The potency of IP₃ formation by acetyl LDL (0.44 nmol/mg protein) was 2‐fold higher than that by native LDL (0.21 nmol/mg protein). Time course studies showed that a maximal effect of IP₃ formation by acetyl LDL at concentrations of 30 μg/ml was observed at 3 min. Longer incubation diminished IP₃ formation. Oxidized LDL also stimulated IP₃ formation with a similar efficiency to acetyl LDL. It was indicated that chemically modified LDL which were taken up through the scavenger receptor pathway activated the macrophages by mediating the phosphatidylinositol hydrolysis and IP₃ formation.