LIPOPROTEIN-LIPASE STIMULATES THE BINDING AND UPTAKE OF MODERATELY OXIDIZED LOW-DENSITY-LIPOPROTEIN BY J774 MACROPHAGES

Lipoprotein lipase (LPL) stimulates the uptake of low-density lipoprot ein (LDL) and very-low-density lipoprotein (VLDL) in different cell ty pes, including macrophages, through bridging of LPL between lipoprotei ns and extracellular heparan sulphate proteoglycans (HSPG). Because ma crophages produce LPL and because modified lipoproteins are present in the arterial wall in vivo, we wondered whether LPL also enhances the uptake of oxidized LDL by J774 macrophages. LDL samples with different degrees of oxidation, as evaluated by relative electrophoretic mobili ty (REM) as compared with native LDL are used, as well as native and a cetylated LDL. Addition of 5 mu g/ml LPL to the J774 cell culture medi um stimulated the binding of both native LDL and moderately oxidized L DL (REM < 3.5) 50-100-fold, and their uptake was stimulated approx. 20 -fold. The LPL-mediated binding of native LDL and moderately oxidized LDL was dose-dependent. Preincubation of the cells with heparinase (2. 4 units/ml) inhibited the stimulatory effect of LPL, indicating that t his LPL-mediated stimulation was due to bridging between the lipoprote ins and HSPG. The binding to 5774 macrophages of severely oxidized LDL (REM = 4.3) was stimulated less than 3-fold by LPL, whereas its uptak e was not stimulated significantly, The binding and uptake of acetylat ed LDL (AcLDL) were not stimulated by LPL, although the LPL-molecule i tself does bind to AcLDL. Measurements of the cellular lipid content s howed that addition of LPL also stimulated the accumulation in the cel ls of cholesteryl ester derived from both native LDL and moderately ox idized LDL in a dose-dependent manner. We conclude that our results pr esent experimental evidence for the hypothesis that LPL serves as an a therogenic component in the vessel wall.