The mechanism of cytolysis of erythrocytes by the mushroom toxin phallolysin. Morphological and biochemical evidence for sodium influx and swelling

Abstract

Phallolysin, a basic protein of multiple molecular forms, was isolated from the mushroom Amanita phalloides. The toxic protein causes cytolysis in most mammalian cells at concentrations as low as 10(-8) M. Different from the cytolytic activities of detergents or sea-anemone toxin, cytolysis by low concentrations of phallolysin occurs only after a lag time of 2 to 3 minutes. In erythrocytes it was shown that phallolysin causes a rapid influx of sodium ions accompanied by a loss of potassium ions. Simultaneously, the cells swell up to their critical volume until they burst. In morphological studies the disruption of red blood cells following phallolysin treatment was found to be indistinguishable from that caused by incubation in hypotonic medium. Freeze-etching studies of phallolysin-treated erythrocytes showed changes in the membrane structure and a decrease of intramembranous particles. It is suggested that phallolysin either forms or opens preformed cation channels in the plasma membrane resulting in cation leakage. Concomitantly with the ion fluxes, water penetrates and causes the cells to swell until lysis occurs.