Modulation of CD4 by suramin

Abstract

SUMMARYSuramin is a polysulphonaled compound which can selectively bind to. and inhibit ihe activity of. a wide range of growth factors. There has been renewed interest rccenlly in suramin as an anti-cancer agent and therefore we have studied its effects on lymphocyte subset populations and recombinant human IL-2 (rhlL-2) activation on lymphocytes in vitro. In tlie presence of rhlL-2 (1000 U/ml), suramin (200 /tg/ml) caused a decrease in percentage of eells expressing the predominantly T cell antigen CD3; no change in percentage of cells expressing the Tsuppressor/cytotoxic subset antigen. CDS; 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 (48-5r:-.. ier.\us 27-97%; P<()00\). CD4 modulation by suramin was also found on the CD4' cell lines CEM and MOLT-4. The effect of suramin on rhlL-2-indueed activation antigen expression remains equivocal, sinee a small rise in CD25 expression and small falls in CD71 and ilLA-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-indueed modulation, but not PMA-induced modulation, could be partially inhibited by preineubation with lyrphostin (12 fM). a tyrosine kinase inhibitor.