Neutralization of the anionic sites of cultured rat mesangial cells by poly-L-lysine

Changes in eicosanoid synthesis are a feature of the functional response of rat glomerular epithelial cells to neutralization of the cell surface polyanion. In order to ascertain if this property is common to other glomerular cell types, we have investigated the effect of neutralization of the negatively charged sites of cultured rat mesangial cells by poly-L-lysine on prostaglandin E2 (PGE2) production. Addition of poly-L-lysine (10 micrograms/ml) to the cells stimulated PGE2 synthesis after an initial latency of approximately two minutes, reaching maximum levels at 60 minutes. Poly-L-lysine also progressively increased cytosolic free calcium ([Ca2+]i) in fura-2 loaded monolayers with a similar initial lag time. Poly-L-lysine-evoked PGE2 synthesis and [Ca2+]i increases were dose dependent and prevented by addition of the polyanions, heparin and albumin. Additionally, heparin was also capable of reversing the effect of poly-L-lysine on [Ca2+]i. Removal of extracellular Ca2+ prevented the increase of [Ca2+]i and PGE2 synthesis. Increased PGE2 synthesis following neutralization of mesangial cell anionic sites may play a role in the hemodynamic dysfunction and cellular derangements of glomerular inflammation.