Cc. Termeer et al., The low molecular weight Dextran 40 inhibits the adhesion of T lymphocytesto endothelial cells, CLIN EXP IM, 114(3), 1998, pp. 422-426
Dextrans are complex colloidal macromolecules widely used as haemorrheologi
c substances and anti-thrombotic agents. Here we describe a navel function
of Dextran 40 by demonstrating an inhibition of T lymphocyte adhesion to en
dothelial cells (EC). We applied an established microassay in which constit
utive and tumour necrosis factor-alpha (TNF-alpha)-induced binding of mouse
T lymphoma cells (TK-I) to mouse endothelioma (eEND.2) cells is mediated b
y the interaction of intercellular adhesion molecule-1 (ICAM-1) and vascula
r 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 therapeu
tically achievable levels (2-32 mg/ml) reduced both constitutive and TNF-al
pha-stimulated TK-1 adhesion to eEND.2. Selective pre-incubation of eEND.2
or TK-1 revealed that Dextran 40 acted exclusively on the T cells. To explo
re further the mechanisms by which Dextran 40 interfered with TK-I adhesion
, their LFA-I and VLA-4 expression was analysed by FAGS. The surface expres
sion levels of neither receptor were affected by Dextran 40. However, confo
cal microscopy revealed that Dextran 40 interfered with the activation-depe
ndent 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 interventi
on in diseases associated with enhanced T lymphocyte binding to microvascul
ar endothelium.