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

Eur J Immunol. 1999 Feb;29(2):563-70. doi: 10.1002/(SICI)1521-4141(199902)29:02<563::AID-IMMU563>3.0.CO;2-A.


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 presence of L-MDP and further processed for apoptosis detection. The highly characteristic 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-stimulating factor protects dendritic cells not only from apoptosis induced by the exogenous compound but also from spontaneous apoptosis. Western blot analysis revealed that this protection was tightly correlated with the activation of a Bcl-2-mediated pathway. Regulation of the apoptotic threshold of dendritic cells will be advantageous for the generation of new insights in immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Non-Narcotic / administration & dosage*
  • Animals
  • Apoptosis / drug effects*
  • Cells, Cultured
  • Clodronic Acid / administration & dosage*
  • Dendritic Cells / metabolism
  • Dendritic Cells / pathology*
  • Drug Carriers
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology*
  • Liposomes
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects


  • Analgesics, Non-Narcotic
  • Drug Carriers
  • Liposomes
  • Proto-Oncogene Proteins c-bcl-2
  • Clodronic Acid
  • Granulocyte-Macrophage Colony-Stimulating Factor