Modulation of CD4 by suramin.
Suramin is a polysulphonated compound which can selectively bind to, and inhibit the activity of, a wide range of growth factors. There has been renewed interest recently in suramin as an anti-cancer agent and therefore we have studied its effects on lymphocyte subset populations and recombinant human IL-2 (rhIL-2) activation on lymphocytes in vitro. In the presence of rhIL-2 (1000 U/ml), suramin (200 micrograms/ml) caused a decrease in percentage of cells expressing the predominantly T cell antigen CD3; no change in percentage of cells expressing the T suppressor/cytotoxic subset antigen, CD8; a small rise in those expressing the natural killer cell antigen, CD56; and a large significant fall in those expressing the T helper subset antigen CD4 (48.51% versus 27.97%; P < 0.001). CD4 modulation by suramin was also found on the CD4+ cell lines CEM and MOLT-4. The effect of suramin on rhIL-2-induced activation antigen expression remains equivocal, since a small rise in CD25 expression and small falls in CD71 and HLA-Dr expression were recorded. The modulatory effect of suramin on CD4 expression was not reversible over a 96-h culture period in its continued presence. However, on removal of suramin by extensive washing, recovery of CD4 expression was detected within 24 h. Suramin-induced modulation, but not PMA-induced modulation, could be partially inhibited by preincubation with tyrphostin (12 microM), a tyrosine kinase inhibitor.
Allen
P D
PD
Department of Surgery, Royal London Hospital, UK.
Johnston
D H
DH
Macey
M G
MG
Williams
N S
NS
Newland
A C
AC
D015704:CD4 Antigens / Q000032:analysis*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D013498:Suramin / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D015704:CD4 Antigens; D007376:Interleukin-2; D011994:Recombinant Proteins; D013498:Suramin; D013755:Tetradecanoylphorbol Acetate