Induction of cell surface blebbing by increased cellular Pi concentration.

Cell surface blebbing is an early, reversible characteristic of anoxia described in several different cell types. Blebbing may lead to the formation of large terminal blebs, and ultimately cell death upon rupture of the membrane. In the present work, evidence is presented indicating that Pi may be the immediate mediator of cell surface blebbing: (1) cell surface blebbing can be induced in normoxic Ehrlich ascites tumour cells by a high extracellular concentration of Pp leading to an increase in the cellular Pi concentration; (2) anoxia induces sustained elevation of the cellular Pi concentration and (3) cell surface blebbing during anoxia is reversed upon reoxygenation, and the disappearance of blebbing depends on the decrease in cellular Pi concentration. The rate of disappearance of blebs may be enhanced by the simultaneous addition of adenine and inosine to the growth medium. This leads to a decrease in cellular Pi concentration and to an almost complete restoration of the cellular ATP concentration. It is suggested that Pi is an important mediator of anoxia induced cell damage.