ACTIVATION OF PROTEIN-KINASE-C BY PHORBOL ESTERS DISRUPTS THE TEGUMENT OF SCHISTOSOMA-MANSONI

The tegument of the human parasite Schistosoma mansoni is critical for parasite survival within the mammalian host. The role of protein kina se C (PKC), a major effector molecule in the phosphoinositide pathway, in maintaining the structural organization of this syncytial layer wa s examined in adult worms. Phorbol 12-myristate, 13-acetate (PMA) and phorbol 12,13-dibutyrate (PDB), phorbol eaters that activate PKC, indu ced formation of surface vesicles as determined by light and scanning electron microscopy. Similar results were seen with sn-2-dioctanoyl-gl ycerol, a synthetic analogue of diacylglycerol. No effect was seen in parasites incubated with 4-alpha-phorbol ester or alpha isomers of PMA or PDB, compounds that do not activate PKC. Vesicle formation was rev ersible in parasites treated with sn-2-dioctanoyl-glycerol but not wit h phorbol esters. The tegument of male worms was more sensitive to the effect of phorbol esters than females. Transmission electron microsco py revealed vacuolization of the tegument. These data suggest that sig nal transduction pathways may have a critical role in the maintenance of the structural integrity of the tegument of parasitic helminths.