Nozaki S, Kashiwagi H, Yamashita S, Nakagawa T, Kostner B, Tomiyama Y, Nakata A, Ishigami M, Miyagawa J, Kameda-Takemura K
Second Department of Internal Medicine, Osaka University Medical School, Japan.
J Clin Invest. 1995 Oct;96(4):1859-65. doi: 10.1172/JCI118231.
To clarify the physiological roles of CD36 as an oxidized low density lipoprotein (OxLDL) receptor, we analyzed the monocyte-derived macrophages from normal and two CD36-deficient subjects, since we identified the molecular abnormalities (Kashiwagi, H., Y. Tomiyama, Y. Kosugi, M. Shiraga, R. H. Lipsky, Y. Kanayama, Y. Kurata, and Y. Matsuzawa 1994. Blood. 83:3545-3552; and Kashiwagi, H., Y. Tomiyama, S. Honda, S. Kosugi, M. Shiraga, N. Nagao, S. Sekiguchi, Y. Kanayama, Y. Kurata, and Y. Matsuzawa. 1995. J. Clin. Invest. 95:1040-1046). Scatchard analysis of 125I-OxLDL binding showed a linear plot and the maximum binding was lower by approximately 40% in the macrophages from subjects with CD36 deficiency than those from normal controls. Competition studies showed that the uptake of 125I-OxLDL was suppressed by OKM5, an antibody against CD36, by 53% in normal control macrophages, but not in the CD36-deficient macrophages. After incubation with OxLDL for 24 h, cholesteryl ester mass accumulation was reduced by approximately 40% in the macrophages from CD36-deficient subjects than those from normal controls. These results suggest that CD36 is one of the physiological receptors for OxLDL. Since specific binding of OxLDL was only reduced by approximately 40% in spite of the complete deficiency of CD36, several other receptors also may have some role in OxLDL uptake. Further studies will be needed to assess the quantitative role of CD36 in foam cell formation in vivo.
为阐明CD36作为氧化型低密度脂蛋白（OxLDL）受体的生理作用，我们分析了来自正常人和两名CD36缺陷受试者的单核细胞衍生巨噬细胞，因为我们已鉴定出分子异常情况（柏木博，富山洋，小杉洋，志贺正，利普斯基RH，金山洋，仓田洋，松泽洋。1994年。《血液》。83:3545 - 3552；以及柏木博，富山洋，本田幸，小杉诚，志贺正，长尾直，关口诚，金山洋，仓田洋，松泽洋。1995年。《临床研究杂志》。95:1040 - 1046）。对125I - OxLDL结合的Scatchard分析显示为线性图，且CD36缺陷受试者的巨噬细胞中最大结合量比正常对照者低约40%。竞争研究表明，抗CD36抗体OKM5可抑制正常对照巨噬细胞中125I - OxLDL的摄取达53%，但对CD36缺陷巨噬细胞无此作用。与OxLDL孵育24小时后，CD36缺陷受试者的巨噬细胞中胆固醇酯质量积累比正常对照者减少约40%。这些结果表明CD36是OxLDL的生理受体之一。尽管CD36完全缺失，但OxLDL的特异性结合仅降低了约40%，因此其他几种受体可能在OxLDL摄取中也发挥一定作用。需要进一步研究来评估CD36在体内泡沫细胞形成中的定量作用。
