A POSSIBLE IMMUNOSUPPRESSANT, CYCLOPRODIGIOSIN HYDROCHLORIDE, OBTAINED FROM PSEUDOALTEROMONAS DENITRIFICANS

Cycloprodigiosin hydrochloride (cPrG.HCl), a member of the prodigiosin family, is a red pigment obtained from the marine bacterium Pseudoalt eromonas denitrificans. cPrG.HCl markedly suppressed H-3-thymidine inc orporation by concanavalin A stimulated murine splenocytes but had Lit tle effect on lipopolysaccharide dependent H-3-thymidine incorporation , indicating that cPrG.HCl acts as a selective inhibitor of T cell pro liferation in the same way as other members of the prodigiosin family. cPrG.HCl inhibited the proliferation of the PMA stimulated Jurkat cel ls through an apoptotic process. Intriguingly, cPrG.HCl inhibited the H+ translocation by vacuolar type ATPase in chromaffin granule membran es without any effect on either its ATPase activity nor on the membran e conductance of phospholipid bilayers, suggesting that cPrG.HCl selec tively uncouples H+ translocation from the ATPase reaction rather than acting as a non-specific ionophore. Since crystalline cPrG.HCl is hig hly stable, it raises the possibility of its therapeutic use as an imm unosuppressant. (C) 1991 Academic Press.