Dextran sulfate specifically interacts with the human LFA-1 molecule (leucocyte function associated antigen-1).

Abstract

We have investigated by flow cytometry the action of dextran sulfate (DxS) on the expression of the LFA-1 molecule in human lymphocytes. This work was undertaken because of the involvement of the LFA-1 molecule in HIV-1 induced syncytia and because of the role of DxS played in the inhibition of syncytia formation. Firstly we detected five distinct topographic regions (epitopes) on the LFA-1 molecule with a panel of 11 monoclonal antibodies (Mabs). Then we demonstrated that DxS interacts with some epitopes mainly present on the alpha chain of the LFA-1 molecule. This inhibition on the LFA-1 expressions by DxS occurs after 1-3 hr of incubation of either 4 or 37 degrees C with complete reappearance of LFA-1 within 1 hr of placing cells in fresh medium. In addition both 5 and 500 kDa have been found to have a similar influence on the inhibition of the LFA-1 expression, while non sulfated dextran have no effect. Other sulfated polyanion (SP) such as heparin and chondroitin sulfate have no effect on the LFA-1 expression. Further at 4 degrees C, DxS does not alter the expression of molecules recognized by Mab such as Leu3a (CD4), Leu2a (CD8), Leu4 (CD3) and Leu5b (CD2). However at 4 degrees C, DxS decreases the expression of CD45R molecule which is recognized by Mab Gap8.3. At 37 degrees C, we observe a decrease also in CD4 expression after DxS exposure. It has also been found that DxS decreases LFA-1 expression to the same extent regardless of the basal expression of LFA-1 in each selected cell subset (LFA-1 low, dim or bright). These results suggest that the inhibitory effect of DxS on the HIV-induced syncytium formation could be due partially to a specific steric hindrance of some LFA-1 determinants.