Inhibition of Fas-induced apoptotic cell death by osmotic cell shrinkage.

Apoptosis is an active physiological mechanism permitting the elimination of cells by triggering an intracellular signalling cascade. Here, we tested whether osmotic alterations of cell volume interfere with apoptotic cell death in Jurkat T-lymphocytes. Apoptotic cell death of Jurkat cells was elicited by activation of the Fas receptor which results in sphingomyelinase stimulation, release of ceramide, activation of Ras, Rac-proteins and formation of O2. Osmotic cell shrinkage inhibited apoptotic cell death induced by the Fas receptor in Jurkat T-lymphocytes. Osmotic cell shrinkage did not interfere with Fas induced activation of the acidic sphingomyelinase or activation of Ras but impaired the formation of O2 suggesting an important function of cell volume in the synthesis of reactive oxygen intermediates upon Fas receptor ligation.