Mechanism of inhibitory effect of dextran sulfate and heparin on human T-cell lymphotropic virus type I (HTLV-I)-induced syncytium formation in vitro: role of cell-to-cell contact.
Cell-to-cell contact is usually essential for syncytium formation by HTLV-I-infected cell lines. The present study was undertaken to determine the inhibitory effect of polyanionic compounds, dextran sulfate and heparin, on HTLV-I-induced syncytium formation, as demonstrated by the fusion of HTLV-I-infected cells with target cells. These two compounds almost completely blocked syncytium formation in the early phase of the reaction at a concentration of 125 micrograms/ml, but dextran, as a control, did not inhibit it at concentrations up to 625 micrograms/ml. 50% inhibition of syncytium formation was detected at a concentration of 2 micrograms/ml of dextran sulfate 5000, 3 micrograms/ml of dextran sulfate 8000 and 8 micrograms/ml of heparin. The binding of radiolabeled HTLV-I-infected cells (HCT-1) to the target cells was inhibited by addition of dextran sulfate and heparin, and the inhibitory effects were concentration-dependent. No marked changes were detected in the expression of adhesion molecules on the virus-infected cells and target cells, and in the expression of envelope proteins on the virus-infected cells after exposing them to the polyanionic compounds. These results suggest that the blocking of cell-to-cell contact by polyanionic compounds, probably independent of surface adhesion molecules, is important for their inhibitory effect on HTLV-I-induced syncytium formation.
Ida
H
H
First Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Kurata
A
A
Eguchi
K
K
Yamashita
I
I
Nakashima
M
M
Sakai
M
M
Kawabe
Y
Y
Nakamura
T
T
Nagataki
S
S
D000911:Antibodies, Monoclonal; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000032:analysis; D002450:Cell Communication / Q000187:drug effects* / Q000502:physiology; D002459:Cell Fusion / Q000187:drug effects / Q000502:physiology; D002461:Cell Line, Transformed; D016264:Dextran Sulfate / Q000494:pharmacology*; D015686:Gene Products, env / Q000032:analysis; D015683:Gene Products, gag / Q000032:analysis; D015726:Giant Cells / Q000187:drug effects*; D015481:HTLV-I Antibodies / Q000097:blood; D015486:HTLV-I Antigens / Q000032:analysis; D006493:Heparin / Q000494:pharmacology*; D006583:Hexadimethrine Bromide / Q000494:pharmacology; D015368:Human T-lymphotropic virus 1 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000276:immunology; D015493:Paraparesis, Tropical Spastic / Q000276:immunology; D015682:Retroviridae Proteins, Oncogenic / Q000032:analysis; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D015686:Gene Products, env; D015683:Gene Products, gag; D015481:HTLV-I Antibodies; D015486:HTLV-I Antigens; D015682:Retroviridae Proteins, Oncogenic; C055266:gp46 protein, Human T-cell leukemia virus type I; D018799:Intercellular Adhesion Molecule-1; D006583:Hexadimethrine Bromide; D006493:Heparin; D016264:Dextran Sulfate