Influence of sulfated carbohydrates on the accessibility of CD4 and other CD molecules on the cell surface and implications for human immunodeficiency virus infection.
The modulatory activity of dextran sulfate with a relative molecular mass of 8 and 500 kDa and pentosan polysulfate with a relative molecular mass of 6 kDa on human T cell surface molecules CD2, CD3, CD4, CD8 and HLA-DR was investigated by analytical flow cytometry. The 500-kDa dextran sulfate induces a complete disappearance of the CD4 and a 50% diminution of CD2 immune reactivity on peripheral blood lymphocytes after a 4-h incubation while the low molecular mass polyanions do not. This modulation of the CD4 immune reactivity includes all CD4 epitopes investigated. It does not correlate with the antiviral effect of polyanions against human immunodeficiency virus infection. The interaction of polyanions with the CD4 presentation is temperature dependent and differs between fresh lymphocytes and immortal cell lines. From our data it can be concluded that mechanisms other than cell surface effects are responsible for the antiviral potency of these drugs. Implications for the modes of antiviral action of sulfated carbohydrates are discussed.
Thiele
B
B
AIDS-Center, Robert-Koch-Institut, Berlin, FRG.
Braig
H R
HR
Ehm
I
I
Kunze
R
R
Ruf
B
B
D000911:Antibodies, Monoclonal / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000382:microbiology*; D016264:Dextran Sulfate; D003911:Dextrans / Q000494:pharmacology*; D006678:HIV / Q000254:growth & development*; D006801:Humans; D066298:In Vitro Techniques; D008970:Molecular Weight; D000071228:Polyelectrolytes; D011108:Polymers / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013431:Sulfates / Q000494:pharmacology*; D013696:Temperature
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D016264:Dextran Sulfate; D003911:Dextrans; D000071228:Polyelectrolytes; D011108:Polymers; D013431:Sulfates