DISTINCT MURINE MACROPHAGE RECEPTOR PATHWAY FOR HUMAN TRIGLYCERIDE-RICH LIPOPROTEINS
DISTINCT MURINE MACROPHAGE RECEPTOR PATHWAY FOR HUMAN TRIGLYCERIDE-RICH LIPOPROTEINS
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DOI：
10.1172/jci113775
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发表时间：
1988-11-01
影响因子：
15.9
通讯作者：
BRADLEY, WA
中科院分区：
文献类型：
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作者：
GIANTURCO, SH;LIN, AHY;BRADLEY, WA
鼠P388 D1巨噬细胞具有与人高脂血症极低密度脂蛋白（HTG-VLDL）结合的受体途径，该受体途径与LDL受体途径根本不同。胰蛋白酶处理的HTG-VLDL（tryp-VLDL），缺乏载脂蛋白（apo）-E，不能与LDL受体结合，但tryp-VLDL和HTG-VLDL交叉竞争与P388 D1巨噬细胞受体结合，表明这些脂蛋白结合相同的位点。胰蛋白酶-VLDL和HTG-VLDL与巨噬细胞的特异性、高亲和力结合在4 ° C。C是等效的，在37 °。C两者都在巨噬细胞中产生快速、大量、曲线（受体介导的）甘油三酯积累。配体印迹显示P388 D1巨噬细胞表达λ的膜蛋白。190 kD（MBP 190），结合胰蛋白酶-VLDL和HTG-VLDL;这种结合被HTG-VLDL、胰蛋白酶化HTG-VLDL和胰蛋白酶化正常VLDL竞争，但不被正常VLDL或LDL竞争。巨噬细胞LDL受体（. 130 kD）和β-葡聚糖的细胞摄取。当细胞暴露于脂蛋白缺乏培养基时，VLDL被诱导，而MBP 190和胰蛋白酶-VLDL的摄取均未被诱导，当细胞装载胆固醇时，VLDL被诱导降低。与巨噬细胞LDL受体不同，MBP 190在Triton X-114提取物相分离后分配到水相中。抗LDL受体多克隆抗体阻断HTG-VLDL与LDL受体的结合并阻断受体介导的β-LDL摄取。P388 D1细胞对胰蛋白酶-VLDL的特异性摄取，但不能抑制胰蛋白酶-VLDL的特异性细胞摄取或阻断胰蛋白酶-VLDL与MBP 190的结合。人单核细胞，但不是人成纤维细胞，也表达类似于MBP 190的GTG-VLDL和胰蛋白酶-VLDL的结合蛋白。我们的结论是，巨噬细胞具有受体异常的人富含磷脂酰肌醇的脂蛋白是不同的LDL受体的配体特异性，调节免疫学特性，和细胞分布。MBP 190具有这些特性，是巨噬细胞高亲和力摄取富含TG的脂蛋白的可能受体候选物。
Murine P388D1 macropphages have a receptor pathway that binds human hypertriglyceridemic very low density lipoproteins (HTG-VLDL) that is fundamentally distinct from the LDL receptor pathway. Trypsin-treated HTG-VLDL (tryp-VLDL), devoid of apolipoprotein (apo)-E, fail to bind to the LDL receptor, yet tryp-VLDL and HTG-VLDL cross-compete for binding to P388D1 macrophage receptors, indicating that these lipoproteins bind to the same sites. The specific, high affinity binding of tryp-VLDL and HTG-VLDL to macrophages at 4.degree. C is equivalent and at 37.degree. C both produce rapid, massive, curvilinear (receptor-mediated) triglyceride accumulation in macrophages. Ligand blots show that P388D1 macrophages express a membrane protein of .apprx. 190 kD (MBP190) that binds both tryp-VLDL and HTG-VLDL; this binding is competed by HTG-VLDL, trypsinized HTG-VLDL, and trypsinized normal VLDL but not by normal VLDL or LDL. The macrophage LDL receptor (.apprx. 130 kD) and cellular uptake of .beta.-VLDL, but not MBP 190 nor uptake of tryp-VLDL, are induced when cells are exposed to lipoprotein-deficient medium and decreased when cells are cholesterol loaded. Unlike the macrophage LDL receptor, MBP 190 partitions into the aqueous phase after phase separation of Triton X-114 extracts. An anti-LDL receptor polyclonal antibody blocks binding of HTG-VLDL to the LDL receptor and blocks receptor-mediated uptake of .beta.-VLDL by P388D1 cells but fails to inhibit specific cellular uptake of tryp-VLDL or to block binding of tryp-VLDL to MBP 190. Human monocytes, but not human fifroblasts, also express a binding protein for GTG-VLDL and tryp-VLDL similar to MBP 190. We conclude that macrophages possess receptors for abnormal human triglyceride-rich lipoproteins that are distinct from LDL receptors in ligand specificity, regulation immunological characteristics, and cellular distribution. MBP 190 shares these properties and is a likely receptor candiate for the high affinity uptake of TG-rich lipoproteins by macrophages.