Nakagawa T, Nozaki S, Nishida M, Yakub J M, Tomiyama Y, Nakata A, Matsumoto K, Funahashi T, Kameda-Takemura K, Kurata Y, Yamashita S, Matsuzawa Y
Second Department of Internal Medicine, Osaka University Medical School, Suita, Japan.
Arterioscler Thromb Vasc Biol. 1998 Aug;18(8):1350-7. doi: 10.1161/01.atv.18.8.1350.
CD36 is a glycoprotein with an Mr of 88 kDa that is expressed on platelets, monocytes/macrophages, capillary endothelial cells, and adipocytes. We previously demonstrated that CD36 is involved in the uptake of oxidized low density lipoprotein (OxLDL) by using CD36-deficient macrophages (J Clin Invest. 1995;96:1859). However, the regulation of CD36 expression in human monocyte-derived macrophages has not been fully elucidated. The current study attempted to clarify the effect of OxLDL and cytokines, both of which are present in atherosclerotic lesions and may play an important role in atherogenesis, on the expression of CD36. A cell enzyme-linked immunosorbent assay and flow cytometry were used to detect CD36 protein. A ribonuclease protection assay was used to measure CD36 mRNA in human monocyte-derived macrophages. The expression of CD36 was increased during the differentiation of monocytes to macrophages. Incubation of macrophages with 25 microg/mL OxLDL for 24 hours increased the level of CD36 protein by 56% and that of CD36 mRNA by 58%. Lysophosphatidylcholine did not affect the expression of CD36. The effects of OxLDL were demonstrated in macrophages that had already differentiated to the point where CD36 expression was almost maximal. Interferon-gamma (IFN-gamma) reduced the expression of CD36 in a dose-dependent manner. A concentration of 1000 U/mL IFN-gamma significantly reduced the expression of CD36 protein by 57% and that of CD36 mRNA by 30%. In conclusion, CD36 may be important in the formation of foam cells by induction through its ligand (OxLDL). Moreover, some local factors, such as IFN-gamma, may suppress CD36 expression on macrophages in human atherosclerotic lesions.
CD36是一种分子量为88 kDa的糖蛋白，在血小板、单核细胞/巨噬细胞、毛细血管内皮细胞和脂肪细胞上表达。我们之前通过使用CD36缺陷型巨噬细胞证明了CD36参与氧化型低密度脂蛋白（OxLDL）的摄取（《临床研究杂志》。1995年；96:1859）。然而，人类单核细胞衍生巨噬细胞中CD36表达的调控尚未完全阐明。当前研究试图阐明OxLDL和细胞因子对CD36表达的影响，这两者都存在于动脉粥样硬化病变中，并且可能在动脉粥样硬化形成中起重要作用。采用细胞酶联免疫吸附测定法和流式细胞术检测CD36蛋白。采用核糖核酸酶保护测定法测量人类单核细胞衍生巨噬细胞中的CD36 mRNA。在单核细胞向巨噬细胞分化过程中，CD36的表达增加。用25 μg/mL OxLDL孵育巨噬细胞24小时，可使CD36蛋白水平增加56%，CD36 mRNA水平增加58%。溶血磷脂酰胆碱不影响CD36的表达。OxLDL的作用在已经分化到CD36表达几乎达到最大值的巨噬细胞中得到证实。干扰素-γ（IFN-γ）以剂量依赖方式降低CD36的表达。1000 U/mL IFN-γ的浓度可使CD36蛋白表达显著降低57%，CD36 mRNA表达降低30%。总之，CD36可能通过其配体（OxLDL）诱导在泡沫细胞形成中起重要作用。此外，一些局部因素，如IFN-γ，可能抑制人类动脉粥样硬化病变中巨噬细胞上CD36的表达。
