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Dextran sulfate specifically interacts with the human LFA-1 molecule (leucocyte function associated antigen-1)
C Vermot-Desroches1, D Rigal, J Bernaud
1Laboratoire d'Immunologie, Centre Régional de Transfusion Sanguine, Lyon, France.
Insights
Dextran sulfate (DxS) inhibits the expression of the LFA-1 molecule on human lymphocytes by interacting with specific epitopes. This action may partially explain DxS's role in preventing HIV-1 induced syncytia formation.
Area of Science:
- Immunology
- Virology
- Biochemistry
Background:
- The LFA-1 molecule is implicated in HIV-1 induced syncytia formation.
- Dextran sulfate (DxS) is known to inhibit syncytia formation.
- Understanding the mechanism of DxS action on LFA-1 is crucial for HIV-1 research.
Purpose of the Study:
- To investigate the effect of dextran sulfate (DxS) on LFA-1 molecule expression in human lymphocytes.
- To identify the specific interactions between DxS and LFA-1 epitopes.
- To elucidate the role of DxS in modulating LFA-1 expression relevant to HIV-1 pathogenesis.
Main Methods:
- Flow cytometry was used to analyze LFA-1 expression on human lymphocytes.
- A panel of monoclonal antibodies (Mabs) was employed to identify LFA-1 epitopes.
- Incubation experiments at varying temperatures (4°C and 37°C) assessed the kinetics and specificity of DxS interaction with LFA-1 and other cell surface molecules (CD4, CD8, CD3, CD2, CD45R).
Main Results:
- Dextran sulfate (DxS) was found to interact with specific epitopes on the alpha chain of the LFA-1 molecule, leading to decreased LFA-1 expression.
- This inhibition occurred within 1-3 hours at both 4°C and 37°C, with LFA-1 reappearing upon removal of DxS.
- DxS affected LFA-1 expression similarly across different cell subsets and did not inhibit other lymphocyte surface markers at 4°C, but decreased CD45R and CD4 expression at specific temperatures.
Conclusions:
- Dextran sulfate (DxS) exerts an inhibitory effect on LFA-1 expression through steric hindrance of specific LFA-1 determinants.
- This modulation of LFA-1 expression by DxS likely contributes to its observed inhibitory effect on HIV-1 induced syncytium formation.
- The findings provide insights into the molecular mechanisms underlying DxS's antiviral properties.
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.
