Phosphatidylinositol turnover in human monocyte-derived macrophages by native and acetyl LDL.
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 micrograms/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 micrograms/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.
Ishikawa
Y
Y
First Department of Internal Medicine, Kobe University, School of Medicine, Japan.
Asaoka
Y
Y
Taniguchi
T
T
Tsunemitsu
M
M
Fukuzaki
H
H
D002478:Cells, Cultured; D004587:Electrophoresis, Agar Gel; D006801:Humans; D006868:Hydrolysis; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000378:metabolism; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism; D010716:Phosphatidylinositols / Q000097:blood*
D007295:Inositol Phosphates; D008077:Lipoproteins, LDL; D010716:Phosphatidylinositols; C032629:acetyl-LDL; D015544:Inositol 1,4,5-Trisphosphate