Rios Francisco J O, Jancar Sonia, Melo Ivo B, Ketelhuth Daniel F J, Gidlund Magnus
Laboratórios de Imunofisiopatologia e Imunofarmacologia, Instituto de Ciencias Biomédicas, Universidade de Sao Paulo, Brazil.
Cell Physiol Biochem. 2008;22(5-6):549-56. doi: 10.1159/000185539. Epub 2008 Dec 9.
Scavenger or Fcgamma receptors are important for capture and clearance of modified LDL particles by monocytes/macrophages. Uptake via scavenger receptors is not regulated by intracellular levels of cholesterol and in consequence, macrophages develop into foam cells in the arterial intima. The levels of scavenger receptor CD36 are increased in atherosclerotic lesions and there is evidence that some components of oxLDL auto-regulate the expression of this receptor. Fcgamma receptor expression is increased in cardiovascular diseases but it is not known weather their expression is regulated by oxLDL. The biological properties of oxLDLs vary depending on the degree of oxidation. In the present study we investigated the effect of LDL particles showing extensive or low oxidation (HoxLDL and LoxLDL) on the expression of CD36 and FcgammaRII in a human monocytic cell line (THP-1), differentiated or not to macrophage, and the involvement of PPARgamma. It was found that both forms of oxLDL are able to increase the expression of CD36 and FcgammaRII and that this effect is dependent on the degree of oxidation and of the stage of cell differentiation (monocyte or macrophage). We also showed that the increased expression of FcgammaRII is dependent on PPARgamma whereas that of the CD36 is independent of PPARgamma.
清道夫受体或Fcγ受体对于单核细胞/巨噬细胞捕获和清除修饰的低密度脂蛋白颗粒很重要。通过清道夫受体的摄取不受细胞内胆固醇水平的调节,因此,巨噬细胞会在动脉内膜中发展为泡沫细胞。清道夫受体CD36的水平在动脉粥样硬化病变中升高,并且有证据表明氧化型低密度脂蛋白的某些成分可自动调节该受体的表达。Fcγ受体的表达在心血管疾病中增加,但尚不清楚其表达是否受氧化型低密度脂蛋白的调节。氧化型低密度脂蛋白的生物学特性因氧化程度而异。在本研究中,我们研究了显示广泛氧化或低度氧化的低密度脂蛋白颗粒(高度氧化型低密度脂蛋白和低度氧化型低密度脂蛋白)对人单核细胞系(THP-1)中CD36和FcγRII表达的影响,该细胞系已分化或未分化为巨噬细胞,以及过氧化物酶体增殖物激活受体γ(PPARγ)的参与情况。结果发现,两种形式的氧化型低密度脂蛋白均能够增加CD36和FcγRII的表达,并且这种作用取决于氧化程度和细胞分化阶段(单核细胞或巨噬细胞)。我们还表明,FcγRII表达的增加依赖于PPARγ,而CD36的表达则不依赖于PPARγ。