Granulocyte-macrophage colony-stimulating factor protects dendritic cells from liposome-encapsulated dichloromethylene diphosphonate-induced apoptosis through a Bcl-2-mediated pathway

Liposome-encapsulated dichloromethylene diphosphonate (L-MDP) has been used for depleting cells of the monocyte-macrophage lineage. We have undertaken this study to investigate whether dendritic cells are susceptible to this liposome-encapsulated compound. Dendritic cells were cultured in the presen ce of L-MDP and further processed for apoptosis detection. The highly chara cteristic DNA cleavage into oligonucleosome-sized fragments, incorporation of biotinylated dUTP into DNA strand breaks and the typical ultrastructural features of apoptosis were evident in dendritic cells exposed to the drug. More importantly we demonstrated that granulocyte-macrophage colony-stimul ating factor protects dendritic cells not only from apoptosis induced by th e exogenous compound but also from spontaneous apoptosis. Western blot anal ysis revealed that this protection was tightly correlated with the activati on of a Bcl-2-mediated pathway. Regulation of the apoptotic threshold of de ndritic cells will be advantageous for the generation of new insights in im munotherapy.