Termeer C C, Weiss J M, Schöpf E, Vanscheidt W, Simon J C
Department of Dermatology, University of Freiburg, Freiburg, Germany.
Clin Exp Immunol. 1998 Dec;114(3):422-6. doi: 10.1046/j.1365-2249.1998.00729.x.
Dextrans are complex colloidal macromolecules widely used as haemorrheologic substances and anti-thrombotic agents. Here we describe a novel function of Dextran 40 by demonstrating an inhibition of T lymphocyte adhesion to endothelial cells (EC). We applied an established microassay in which constitutive and tumour necrosis factor-alpha (TNF-alpha)-induced binding of mouse T lymphoma cells (TK-1) to mouse endothelioma (eEND.2) cells is mediated by the interaction of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on EC with their counter-receptors the LFA-1 heterodimer (CD11a/CD18) and VLA-4 on T cells. Dextran 40 in therapeutically achievable levels (2-32 mg/ml) reduced both constitutive and TNF-alpha-stimulated TK-1 adhesion to eEND.2. Selective preincubation of eEND.2 or TK-1 revealed that Dextran 40 acted exclusively on the T cells. To explore further the mechanisms by which Dextran 40 interfered with TK-1 adhesion, their LFA-1 and VLA-4 expression was analysed by FACS. The surface expression levels of neither receptor were affected by Dextran 40. However, confocal microscopy revealed that Dextran 40 interfered with the activation-dependent capping and clustering of LFA-1 and VLA-4 on the surface of TK-1. We conclude that Dextran 40 inhibits the capacity of TK-1 T cells to adhere to eEND.2 endothelial cells and thus may be useful for therapeutic intervention in diseases associated with enhanced T lymphocyte binding to microvascular endothelium.
右旋糖酐是复杂的胶体大分子，广泛用作血液流变学物质和抗血栓形成剂。在此，我们通过证明右旋糖酐40对T淋巴细胞与内皮细胞（EC）黏附的抑制作用，描述了其一种新功能。我们应用了一种既定的微量分析方法，其中小鼠T淋巴瘤细胞（TK-1）与小鼠内皮瘤（eEND.2）细胞的组成性结合以及肿瘤坏死因子-α（TNF-α）诱导的结合是由EC上的细胞间黏附分子-1（ICAM-1）和血管细胞黏附分子-1（VCAM-1）与其在T细胞上的对应受体LFA-1异二聚体（CD11a/CD18）和VLA-4之间的相互作用介导的。治疗可达到水平（2-32mg/ml）的右旋糖酐40降低了组成性和TNF-α刺激的TK-1对eEND.2的黏附。对eEND.2或TK-1进行选择性预孵育表明，右旋糖酐40仅作用于T细胞。为了进一步探究右旋糖酐40干扰TK-1黏附的机制，通过荧光激活细胞分选术（FACS）分析了它们的LFA-1和VLA-4表达。两种受体的表面表达水平均不受右旋糖酐40的影响。然而，共聚焦显微镜显示，右旋糖酐40干扰了TK-1表面LFA-1和VLA-4的激活依赖性帽化和聚集。我们得出结论，右旋糖酐40抑制TK-1 T细胞黏附eEND.2内皮细胞的能力，因此可能有助于对与T淋巴细胞与微血管内皮细胞结合增强相关疾病的治疗干预。
