Lindqvist P, Ostlund-Lindqvist A M, Witztum J L, Steinberg D, Little J A
J Biol Chem. 1983 Aug 10;258(15):9086-92.
We have previously shown that cultured macrophages secrete lipoprotein lipase (LPL) into the culture medium. The purpose of these experiments was to determine the role of LPL in the uptake of very low density lipoproteins (VLDL). Both J774 cells and mouse peritoneal macrophages took up and degraded normotriglyceridemic VLDL in a saturable manner. Uptake of VLDL was effectively competed for by rabbit beta-VLDL, human VLDL, but not by native LDL or acetyl LDL. LPL activity accelerated saturable uptake of VLDL but was not a prerequisite for it. This was most clearly seen in experiments with apo-C-II-deficient VLDL. Although no hydrolysis of VLDL triglyceride occurred, saturable uptake and degradation of the C-II-deficient lipoprotein occurred. However, addition of apo-C-II enhanced saturable uptake. Normal VLDL also promoted cellular accumulation of both triglycerides and cholesteryl esters. Accumulation of triglyceride occurred by uptake of intact VLDL particles, by uptake of a triglyceride-depleted particle produced by the action of LPL, and by the direct uptake of free fatty acids generated by the activity of LPL. In turn, the latter process was influenced by the amount of albumin in the medium capable of being an acceptor for free fatty acids. Finally, we have shown that when albumin is present in the medium, the macrophage is capable of mobilizing most of its stored triglyceride over 24 h, even as its cholesteryl ester content remains constant. These studies may be relevant to the ability of VLDL to promote macrophage accumulation of cholesteryl ester, even as triglyceride accumulation is minimized.
我们之前已经表明，培养的巨噬细胞会将脂蛋白脂肪酶（LPL）分泌到培养基中。这些实验的目的是确定LPL在极低密度脂蛋白（VLDL）摄取中的作用。J774细胞和小鼠腹腔巨噬细胞都以可饱和的方式摄取并降解正常甘油三酯血症的VLDL。VLDL的摄取可被兔β-VLDL、人VLDL有效竞争，但不能被天然LDL或乙酰化LDL竞争。LPL活性加速了VLDL的可饱和摄取，但不是其摄取的先决条件。这在apo-C-II缺陷型VLDL的实验中最为明显。虽然没有发生VLDL甘油三酯的水解，但缺陷型C-II脂蛋白仍可被可饱和摄取和降解。然而，添加apo-C-II可增强可饱和摄取。正常VLDL也促进了甘油三酯和胆固醇酯的细胞内积累。甘油三酯的积累是通过摄取完整的VLDL颗粒、摄取由LPL作用产生的甘油三酯耗尽颗粒以及直接摄取由LPL活性产生的游离脂肪酸而发生的。反过来，后一过程受培养基中能够作为游离脂肪酸受体的白蛋白量的影响。最后，我们已经表明，当培养基中存在白蛋白时，巨噬细胞能够在24小时内动员其大部分储存的甘油三酯，即使其胆固醇酯含量保持不变。这些研究可能与VLDL促进巨噬细胞胆固醇酯积累的能力有关，即使甘油三酯积累降至最低。
