Interaction of a high-affinity heparin subfraction with low-density lipoprotein stimulates cholesteryl ester accumulation in mouse macrophages
| Autor: | Bhandaru Radhakrishnamurthy, Sathanur R. Srinivasan, Gerald S. Berenson, Karen Eberle, Parakat Vijayagopal |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
Phagocytosis
Biophysics Ligands Endocytosis Biochemistry Chromatography Affinity Mice chemistry.chemical_compound Endocrinology Affinity chromatography medicine Animals Scavenger receptor Peritoneal Cavity Heparin Macrophages Osmolar Concentration Lipoproteins LDL chemistry Low-density lipoprotein Cholesteryl ester Female lipids (amino acids peptides and proteins) Cholesterol Esters medicine.drug Lipoprotein |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism. 1081:188-196 |
| ISSN: | 0005-2760 |
| DOI: | 10.1016/0005-2760(91)90025-d |
| Popis: | A high-affinity heparin subfraction accounting for 8% of whole heparin from bovine lung was isolated by low-density lipoprotein (LDL)-affinity chromatography. When compared to whole heparin, the high-affinity subfraction was relatively higher in molecular weight (11 000 vs. 17 000) and contained more iduronyl sulfate as hexuronic acid (76% vs. 86%), N -sulfate ester (0.75 vs. 0.96 mol/mol hexosamine), and O -sulfate ester (1.51 vs. 1.68 mol/mol hexosamine). Although both heparin preparations formed insoluble complexes with LDL quantitatively in the presence of 30 mM Ca 2+ , the concentrations of NaCl required for 50% reduction in maximal insoluble complex formation was markedly higher with high-affinity subfraction (0.55 M vs. 0.04 M). When compared to complex of 125 I-LDL and whole heparin (H- 125 I-LDL), complex of 125 I-LDL and high-affinity heparin subfraction (HAH- 125 I-LDL) produced marked increase in the degradation of lipoproteins by macrophages (7-fold vs. 1.4-fold over native LDL, after 5 h incubation) as well as cellular cholesteryl ester synthesis (16.7-fold vs. 2.2-fold over native LDL, after 18 h incubation) and content (36-fold vs. 2.7-fold over native LDL, after 48 h incubation). After a 5 h incubation, macrophages accumulated 2,3-fold more cell-associated radioactivity from HAH- 125 I-LDL complex than from [ 125 I]acetyl-LDL. While unlabeled HAH-LDL complex produced a dose-dependent inhibition of the degradation of labeled complex, native unlabeled LDL did not elicit any effect even at a 20-fold excess concentration. Unlabeled particulate LDL aggregate completed for 33% of degradation of labeled complex; however, cytochalasin D, known inhibitor of phagocytosis, did not effectively inhibit the degradation of labeled complex. Unlabeled acetyl-LDL produced a partial (33%) inhibition of the degradation of labeled complex. These results indicate that (1) the interaction of high-affinity heparin subfraction with LDL leads to scavenger receptor mediated endocytosis of the lipoprotein, and stimulation of cholesteryl ester synthesis and accumulation in the macrophages; and (2) with respect to macrophage recognition and uptake, HAH-LDL complex was similar but not identical to acetyl-LDL. These observations may have implications for atherogenesis, because both mast cells and endothelial cells can synthesize heparin in the arterial wall. |
| Databáze: | OpenAIRE |
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