Gianturco S H, Ramprasad M P, Lin A H, Song R, Bradley W A
Department of Medicine, University of Alabama at Birmingham 35294-0012.
J Lipid Res. 1994 Sep;35(9):1674-87.
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.
源自单核细胞 - 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。在本报告中，4℃下的直接结合研究表明，从血液中分离1 - 6天后的人单核细胞 - 巨噬细胞（HMM）以及用人佛波酯分化前和分化后长达7天的人THP - 1单核细胞，对某些富含甘油三酯的脂蛋白（TGRLP）的摄取和降解表现出高亲和力（Kd 3 - 6 nM）、可饱和、特异性且不依赖载脂蛋白（apo）E的结合位点。配体印迹分析在两种细胞类型中鉴定出两种表观分子量分别为200和235 kDa的膜结合蛋白（MBP 200和MBP 235），它们与细胞位点具有相同的配体特异性，并且以高亲和力结合高甘油三酯血症（HTG）极低密度脂蛋白（VLDL）、不含apoE的胰蛋白酶消化的VLDL（tryp - VLDL）以及正常受试者的膳食血浆乳糜微粒，但不结合低密度脂蛋白（LDL）、乙酰化LDL或正常VLDL。TGRLP与细胞或分离的MBP结合既不需要脂蛋白脂肪酶也不需要apoE。与LDL或乙酰化LDL受体不同，细胞结合位点和MBP在分化的所有阶段均以相似水平表达。与MBP结合的TGRLP可诱导单核细胞以及巨噬细胞中快速、可饱和的细胞内甘油三酯积累；正常VLDL则不会。此外，与LDL受体不同，细胞高亲和力结合位点以及MBP 200和235不受培养基固醇含量的影响。综上所述，这些数据表明人单核细胞 - 巨噬细胞表现出高亲和力、可饱和、特异性、不依赖apoE和脂蛋白脂肪酶的结合位点以及膜结合蛋白，用于TGRLP，它们在表达、特异性和分子大小上与LDL受体基因家族的受体或乙酰化LDL受体不同。细胞结合位点与MBP 200和MBP 235的共同特征表明它们可能是单核细胞和巨噬细胞介导的、不依赖apoE摄取HTG - VLDL和乳糜微粒的受体候选物，因此可能参与泡沫细胞的形成。
