Effect of polycations on prostaglandin synthesis in cultured glomerular mesangial cells

The presence of uniform negative charges on the surface of cultured rat glomerular mesangial cells was demonstrated by an ultrastructural marker, cationized ferritin. Interaction between cell surface negative charges and protamine sulfate, stimulated the synthesis of prostaglandins E2, F2 alpha, 6-keto-PGF1 alpha and thromboxane B2 (TXB2) in a dose-dependent manner, reaching a maximum response at protamine concentration of 50 micrograms/ml. The effect of protamine sulfate was reversed by 25 units/ml heparin. The polyanions, L-glutamic and L-aspartic acids, reversed the protamine effect in a dose-dependent manner. Excess substrate, arachidonic acid, masked the protamine sulfate-stimulated PGE2 synthesis by mesangial cells. The effect of protamine sulfate on PGE2 synthesis was rapid, peaked in 5 min and was independent of extracellular Ca2+. A synthetic cation, poly(L-lysine) hydrobromide, exerted a similar effect on cellular PGE2 synthesis in mesangial cells. The effect of poly(L-lysine) was dependent on the molecular mass of the cationic species employed and was maximum at 17 to 90 kDa. The use of large molecular mass polymers of L-lysine (175 and 565 kDa) resulted in a decline in PGE2 synthesis. These observation indicate that, in mesangial cells, changes in cell membrane electrical charge are linked to enhanced biosynthetic activity and eicosanoid synthesis.