Cellular binding site and membrane binding proteins for triglyceride-rich lipoproteins in human monocyte-macrophages and THP-1 monocytic cells.
Cellular binding site and membrane binding proteins for triglyceride-rich lipoproteins in human monocyte-macrophages and THP-1 monocytic cells.
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发表时间：
1994-09
影响因子：
6.5
通讯作者：
S. Gianturco;M. Ramprasad;A. Lin;R. Song;W. Bradley
中科院分区：
文献类型：
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作者：
S. Gianturco;M. Ramprasad;A. Lin;R. Song;W. Bradley
来源于单核细胞-巨噬细胞的富含甘油三酯和胆固醇的泡沫细胞通常与某些形式的高甘油三酯血症相关。在这份报告中，在4摄氏度下的直接结合研究表明，从血液中分离的人单核细胞-巨噬细胞（HMM）和人THP-1单核细胞在用佛波醇酯分化之前和分化后长达7天表现出高亲和力。（Kd 3-6 nM），可饱和，特异性，和载脂蛋白（apo）E-非依赖性结合位点，用于摄取和降解某些富含甘油三酯的脂蛋白（TGRLP）。配体印迹分析鉴定了表观分子量为200和235 kDa的两种膜结合蛋白（MBP（MBP 200和MBP 235）在两种细胞类型中具有与细胞位点相同的配体特异性并结合高脂血症（HTG）VLDL、缺乏apoE的胰蛋白酶化VLDL（胰蛋白酶-VLDL）和来自正常受试者的膳食血浆乳糜微粒，但不包括LDL、乙酰LDL或具有高亲和力的正常VLDL。TGRLP与细胞或分离的MBP结合既不需要脂蛋白脂酶也不需要apoE。与LDL或乙酰LDL受体不同，细胞结合位点和MBP在分化的所有阶段都以相似的水平表达。与MBP结合的TGRLP诱导单核细胞和巨噬细胞中快速的、饱和的细胞甘油三酯积累;正常VLDL不会。此外，与LDL受体不同，细胞高亲和力结合位点和MBP 200和235不受培养基甾醇含量的影响。总之，这些数据表明，人单核细胞-巨噬细胞表现出高亲和力，饱和，特异性，apoE和脂蛋白脂肪酶独立的结合位点和膜结合蛋白的TGRLP不同的表达，特异性和分子大小的LDL受体基因家族或乙酰LDL受体的受体。MBP 200和MBP 235的细胞结合位点的共同特征表明，它们是单核细胞和巨噬细胞对HTG-VLDL和乳糜微粒的受体介导的、apoE非依赖性摄取的候选者，因此可能参与泡沫细胞形成。
Triglyceride- and cholesterol-rich foam cells derived from monocyte-macrophages are commonly associated with some forms of hypertriglyceridemia. In this report, direct binding studies at 4 degrees C demonstrate that human monocyte-macrophages (HMM) 1-6 days after isolation from blood and human THP-1 monocytic cells, before and up to 7 days after differentiation with phorbol ester, exhibit a high affinity (Kd 3-6 nM), saturable, specific, and apolipoprotein (apo) E-independent binding site for the uptake and degradation of certain triglyceride-rich lipoproteins (TGRLP). Ligand blotting analysis identified two membrane binding proteins (MBP) of apparent molecular weights of 200 and 235 kDa (MBP 200 and MBP 235) in both cell types that share the same ligand specificity as the cellular site and bind hypertriglyceridemic (HTG) VLDL, trypsinized VLDL devoid of apoE (tryp-VLDL), and dietary plasma chylomicrons from normal subjects but not LDL, acetyl LDL, or normal VLDL with high affinity. Neither lipoprotein lipase nor apoE are required for TGRLP binding to the cells or the isolated MBPs. The cellular binding site and the MBPs are expressed at similar levels at all stages of differentiation, unlike the LDL or the acetyl LDL receptor. TGRLP that bind to the MBPs induce rapid, saturable, cellular triglyceride accumulation in monocytes as well as macrophages; normal VLDL does not. In addition, the cellular high affinity binding site and MBP 200 and 235 are not affected by the media sterol content, unlike the LDL receptor. Taken together, these data indicate that human monocyte-macrophages exhibit a high affinity, saturable, specific, apoE- and lipoprotein lipase-independent binding site and membrane binding proteins for TGRLP that differ in expression, specificity, and molecular size from receptors of the LDL receptor gene family or the acetyl LDL receptor. The shared characteristics of the cellular binding site with MBP 200 and MBP 235 suggest that they are candidates for the receptor-mediated, apoE-independent uptake of HTG-VLDL and chylomicrons by monocytes and macrophages and therefore may be involved in foam cell formation.