Calcium in lymphotoxin-mediated cytolysis: cellular pools, fluxes, and role of extracellular concentration.

This study explores, by kinetic analysis, the movement of calcium among cellular pools of target cells in which cytotoxicity is induced by human lymphotoxin, and evaluates the requirement for calcium in this reaction. We employed the kinetic model of Borle to quantitate flux rates and pool sizes. It was found that the rate of flux between the surface (plasma membrane-glycocalyx) compartment and the intracellular compartment was greatly increased. The size of the total exchangeable intracellular calcium pool was not altered, but there was an apparent decrease in the size of the surface calcium pool. This latter phenomenon may be related to the blebbing and exfoliation of plasma membranes under the influence of the lymphokine. Lymphotoxin-induced cytotoxicity is observed in calcium-free medium and over a range of calcium concentrations. These results argue against cell death due to a massive in rush of calcium into the cell under these circumstances.