EFFECT OF PENTOXIFYLLINE ON APOPTOSIS OF CULTURED-CELLS

Apoptosis or programmed cell death (PCD) was measured in two human cel l models by flow cytometric analysis. Blood neutrophils underwent spon taneous apoptosis in short-term culture. Pentoxifylline (PTX) inhibite d spontaneous neutrophil PCD. We confirmed that granulocyte/macrophage colony-stimulating factor (GM-CSF) inhibited apoptosis of polymorphon uclear neutrophils. Treatment with both GM-CSF and PTX did not increas e the inhibition of PCD by either GM-CSF or PTX alone. Because apoptos is could be due to the accumulation of H2O2 in the culture medium, and because PTX has been described to reduce peroxide production, we stud ied the effect of adding catalase to the medium. Catalase reduced the neutrophil apoptosis and this effect was cumulative with the effect of PTX. Camptothecin, an inhibitor of topoisomerase I, induces a block i n the S-phase of the cell cycle followed by apoptosis of the U937 cell line. This drug-induced apoptosis was partially inhibited by PTX, whe reas the S-phase cell block was not affected. In conclusion, PTX was f ound to inhibit apoptosis in two different human cell types. In neutro phils, this effect appears to occur regardless of the inhibition of ph osphodiesterase activity and inhibition of H2O2 release.