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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.

We have elucidated the structures of N-linked sugar chains of human apolipoprotein (apo) B-100 (Arch Biochem Biophys 1989; 273:197-205). To investigate the role of the carbohydrate moieties of apolipoprotein B-100, we determined the structures of the N-linked sugar chains of apo B-100 purified from low density lipoprotein (LDL) of a Watanabe heritable hyperlipidemic (WHHL) rabbit and compared them with those of fasting Japanese White rabbits. The N-linked oligosaccharides of apo B-100 were liberated by hydrozinolysis, followed by NaB3H4 reduction, and were fractionated by paper electrophoresis and Bio-Gel P-4 column chromatography. These consisted of one neutral fraction (N) and two acidic fractions (A1 and A2) in both WHHL and fasting rabbits. N contained high mannose type oligosaccharides consisting of Man5GlcNAc2 to Man9GlcNAc2. A1 and A2 contained monosialylated and disialylated biantennary complex type oligosaccharides, respectively. The molar ratios of N, A1, and A2 were 5:2:2 in the WHHL rabbit and 4:2:5 in fasting rabbits. The content of sialic acid residues in the WHHL rabbit was calculated to be 0.64 by taking the value of that in fasting rabbits as 1.0. These results show the heterogeneity of N-linked sugar chains of apo B-100 in WHHL and fasting rabbits and suggest the possibility that the characteristics of LDL in WHHL rabbits may be altered by making the surface charge more positive than in fasting rabbits.

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