| Apoptosis is a controlled process of active cellular self-destruction. Enhancement or blockade of intra- and extra cellular pathways leading to apoptosis is promising concepts for the design of novel experimental and therapeutic strategies. In the current work, we investigated specific aspects of apoptosis in two distinct models: during human cytomegalovirus (HCMV) infection in fibroblasts we have found that in a productive HCMV infection of human fibroblasts, loss of cell viability was not only due to the virus-mediated cell lysis but also apoptosis. Infection is associated with expression of Fas-R---which renders infected cells susceptible to Fas-ligand-mediated apoptosis. While Fas-triggering in infected cultures lead to decreased viral output by elimination of HCMV infected cells, interferon-gamma decreased viral output by inhibition of HCMV life cycle, which resulted in the better preservation of cell viability. In addition to its antiviral activity, IFN-gamma primes HCMV infected cells to the action of Fas-L by up modulation of receptor. This experimental system demonstrates that induction of apoptosis of infected cells, may be an important defense mechanism.;In the second part of this work consequences of apoptosis blockade in hematopoietic progenitor and stem cells were studied. CD34+ cells constitutively express essential caspases (-1, -3 & 8). Fas- and serum starvation-induced apoptosis was inhibited using synthetic peptides suppressing specific caspases involved in the apoptotic transduction pathway. We found that caspase blockade was more effective in preventing Fas-mediated apoptosis than those induced by serum withdrawal. Unlike in lymphoid system, in CD34+ cells, specific inhibitor of caspase-1 showed better anti-apoptotic effect then inhibitors of caspase-3. Although blockade of apoptosis in early hematopoietic progenitor and stein cells, prevented their early loss of viability and clonogenic potential, differentiation and the ultimate exhaustion of the progenitor cells in the culture could not be prevented.;Both experimental systems demonstrate that modulation of apoptotic events can be used as investigational tool. Better understanding of apoptosis and its regulation may facilitate development of novel therapeutic strategies in diseases associated either with excess of or resistance to apoptosis. |
