Schonfeld G, Patsch W, Pfleger B, Witztum J L, Weidman S W
J Clin Invest. 1979 Nov;64(5):1288-97. doi: 10.1172/JCI109584.
Smaller very low density lipoprotein (VLDL) remnants interact more readily with tissues than do larger "intact" VLDL. This may be related to changes in the availability of VLDL apoproteins on the surface of the lipoproteins. To test this hypothesis VLDL were incubated at 37 degrees C with bovine milk lipase (LPL), and the abilities of LPL-treated VLDL preparations to compete with (125)I-low density lipoproteins (LDL) for interaction with cultured normal human fibroblasts were measured. At the same time, the immunologic activities of these preparations were also tested by double antibody radioimmunoassay. Triglyceride (TG) contents of VLDL fell by 30-90% during incubation with LPL and, on zonal ultracentrifugation, VLDL of faster Svedberg unit of flotation (S(f1.063)) rates (>150) were gradually converted to smaller VLDL with lower S(f) rates (21-60). LPL-treated VLDL competed two to five times more effectively with (125)I-LDL for binding to cellular receptors than did control VLDL. Control VLDL incubated with heat-inactivated LPL at 37 degrees C, or with active LPL at 4 degrees C had unaltered cell reactivities and TG contents compared with VLDL incubated without any enzyme. The direct uptake and degradation of LPL-treated VLDL was also assessed by using VLDL (125)I-labeled in apoprotein (Apo)B. LPL-treated VLDL-(125)I-ApoB were taken up and degraded by fibroblast at greater rates than were control VLDL-(125)I-ApoB. Thus, hydrolysis of VLDL lipids was accompanied by an increased ability of VLDL to interact with fibroblasts. The immunoreactivity of ApoB in the same VLDL preparations, expressed as the "apparent ApoB contents" of LPL-treated VLDL, increased by 10-50% (P < 0.02) in those assays that contained anti-LDL antisera, but the ApoB of control VLDL remained constant. However, assays that contained antisera directed against ApoB isolated from VLDL did not distinguish between LPL-treated and control VLDL. Thus, VLDL lipid hydrolysis was accompanied by changes in the immunoreactivity of VLDL-ApoB, which probably reflect changes in the disposition of ApoB on the surface of VLDL. The altered disposition of ApoB on VLDL "remnants" may be related to their enhanced interaction with cells.
与较大的“完整”极低密度脂蛋白（VLDL）相比，较小的VLDL残粒与组织的相互作用更为容易。这可能与脂蛋白表面VLDL载脂蛋白的可利用性变化有关。为了验证这一假说，将VLDL与牛胰脂酶（LPL）在37℃孵育，然后测定经LPL处理的VLDL制剂与（125）I-低密度脂蛋白（LDL）竞争与培养的正常人成纤维细胞相互作用的能力。同时，还通过双抗体放射免疫测定法检测了这些制剂的免疫活性。在与LPL孵育期间，VLDL的甘油三酯（TG）含量下降了30%至90%，并且在区带超速离心时，沉降系数（S(f)）较高（>150）的VLDL逐渐转化为沉降系数较低（21-60）的较小VLDL。与对照VLDL相比，经LPL处理的VLDL与（125）I-LDL竞争结合细胞受体的效率提高了2至5倍。与未用任何酶孵育的VLDL相比，在37℃与热灭活的LPL孵育或在4℃与活性LPL孵育的对照VLDL，其细胞反应性和TG含量未发生改变。还通过使用载脂蛋白（Apo）B标记有（125）I的VLDL评估了经LPL处理的VLDL的直接摄取和降解情况。与对照VLDL-（125）I-ApoB相比，经LPL处理的VLDL-（125）I-ApoB被成纤维细胞摄取和降解的速率更高。因此，VLDL脂质的水解伴随着VLDL与成纤维细胞相互作用能力的增强。在那些含有抗LDL抗血清的测定中，相同VLDL制剂中ApoB的免疫反应性，以经LPL处理的VLDL的“表观ApoB含量”表示，增加了10%至50%（P<0.02），但对照VLDL的ApoB保持不变。然而，含有针对从VLDL分离的ApoB的抗血清的测定无法区分经LPL处理的VLDL和对照VLDL。因此，VLDL脂质水解伴随着VLDL-ApoB免疫反应性的变化，这可能反映了ApoB在VLDL表面分布的变化。ApoB在VLDL“残粒”上分布的改变可能与其与细胞增强的相互作用有关。
