Seigneur M, Dufourcq P, Belloc F, Lenoble M, Renard M, Boisseau M R
Laboratory of Hematology, University of Bordeaux II, Bordeaux, France.
J Cardiovasc Pharmacol. 1995;25 Suppl 2:S85-7. doi: 10.1097/00005344-199500252-00018.
Thrombomodulin (TM) expression at the surface of endothelial cells is upregulated by cAMP analogues, whereas hypoxic conditions induce a decrease in this expression. Pentoxifylline (PTX) enhances the intracellular levels of cAMP in human umbilical vein endothelial cells (HUVECs). We therefore investigated the influence of this drug on TM expression in cells submitted to hypoxia. TM expression was quantified at the surface of HUVECs in the presence or absence of PTX during 18 h of incubation. Membrane TM was immunolabeled with a fluorescent monoclonal antibody and the expression was quantified by flow cytometric analysis. Our preliminary data revealed that PTX at 0.01 microM significantly increased TM expression levels compared with cells in hypoxia without the drug. Therefore, at this low dose PTX appears able to counterbalance the procoagulant effect of hypoxia.
内皮细胞表面的血栓调节蛋白(TM)表达可被环磷酸腺苷(cAMP)类似物上调,而低氧条件会导致该表达下降。己酮可可碱(PTX)可提高人脐静脉内皮细胞(HUVECs)内的cAMP水平。因此,我们研究了这种药物对处于低氧状态的细胞中TM表达的影响。在有无PTX的情况下,对HUVECs进行18小时孵育,然后对其表面的TM表达进行定量。用荧光单克隆抗体对膜TM进行免疫标记,并通过流式细胞术分析对表达进行定量。我们的初步数据显示,与未使用药物处于低氧状态的细胞相比,0.01微摩尔的PTX可显著提高TM表达水平。因此,在这个低剂量下,PTX似乎能够抵消低氧的促凝血作用。