Juompan L, Puel J, Fournié G J, Benoist H
INSERM U 395, Université Paul Sabatier, Toulouse, France.
Biochim Biophys Acta. 1995 Aug 15;1272(1):21-8. doi: 10.1016/0925-4439(95)00053-7.
Activated lymphocytes have a high level of low density lipoprotein (LDL) uptake as compared to resting lymphocytes, whereas scavenger receptors for acetylated LDL (Ac-LDL) are expressed on limited number of immune cells, i.e., monocytes/macrophages. The endocytosis of LDL and Ac-LDL by mononuclear cells was studied during in vitro and in vivo HIV infection, in order to use LDL and Ac-LDL as carriers of antiviral and/or immunomodulatory drugs towards lymphocytes and monocytes. The uptake of LDL and Ac-LDL was analyzed by cytofluorimetry. LDL endocytosis in PHA/IL2-activated lymphocytes was higher than in resting lymphocytes. In vitro HIV infection of PHA/IL2-activated lymphocytes did not alter the high LDL endocytosis in lymphocytes. CD4+ and CD8+ cells. In a group of 12 symptomatic patients there was no alteration of LDL endocytosis in lymphocytes, CD4 and CD8 lymphocytes. In another group of 23 individuals, the Ac-LDL endocytosis mediated by CD14+ monocytes was unaltered in asymptomatic patients (n = 6) and in some symptomatic patients (n = 6, CD14+ cells > 100/mm3). On the contrary, in other symptomatic patients (n = 11, CD14+ cells < 100/mm3), the number of Ac-LDL+ CD14+ cells decreased, whereas their efficiency of Ac-LDL endocytosis increased as compared to those of other HIV+ patients. In conclusion, the use of lipoproteins as carriers to increase the drug delivery to CD4+ lymphocytes and to CD14+ monocytes can be envisaged, since: (i) the LDL endocytosis was not impaired in CD4 lymphocytes of HIV+ patients, and (ii) the Ac-LDL uptake by monocytes was altered only in some patients of stage IV.
与静息淋巴细胞相比，活化淋巴细胞对低密度脂蛋白（LDL）的摄取水平较高，而乙酰化LDL（Ac-LDL）的清道夫受体仅在有限数量的免疫细胞即单核细胞/巨噬细胞上表达。为了将LDL和Ac-LDL用作抗病毒和/或免疫调节药物向淋巴细胞和单核细胞的载体，研究了体外和体内HIV感染期间单核细胞对LDL和Ac-LDL的内吞作用。通过细胞荧光测定法分析LDL和Ac-LDL的摄取。PHA/IL2活化淋巴细胞中的LDL内吞作用高于静息淋巴细胞。PHA/IL2活化淋巴细胞的体外HIV感染并未改变淋巴细胞中较高的LDL内吞作用，包括CD4+和CD8+细胞。在一组12名有症状的患者中，淋巴细胞、CD4和CD8淋巴细胞中的LDL内吞作用没有改变。在另一组23名个体中，无症状患者（n = 6）和一些有症状患者（n = 6，CD14+细胞>100/mm3）中由CD14+单核细胞介导的Ac-LDL内吞作用未改变。相反，在其他有症状患者（n = 11，CD14+细胞<100/mm3）中，Ac-LDL+ CD14+细胞数量减少，而与其他HIV+患者相比，其Ac-LDL内吞效率增加。总之，可以设想使用脂蛋白作为载体来增加药物向CD4+淋巴细胞和CD14+单核细胞的递送，因为：（i）HIV+患者的CD4淋巴细胞中的LDL内吞作用未受损，以及（ii）仅在IV期的一些患者中单核细胞对Ac-LDL的摄取发生改变。
