Depletion and repopulation of macrophages in spleen and liver of rat after intravenous treatment with liposome-encapsulated dichloromethylene diphosphonate

Cell Tissue Res. 1990 May;260(2):215-22. doi: 10.1007/BF00318625.


Rats received a single intravenous injection with liposome-encapsulated dichloromethylene diphosphonate (C12MDP). This treatment resulted in the elimination of macrophages in spleen and liver within 2 days. Macrophages ingest the liposomes and are destroyed by the drug, which is released from the liposomes after disruption of the phospholipid bilayers under the influence of lysosomal phospholipases. Repopulation of macrophages in spleen and liver was studied at different time intervals after treatment. Macrophages in the liver (Kupffer cells) and red pulp macrophages in the spleen were the first cells to reappear, followed by marginal metallophilic macrophages and marginal-zone macrophages in the spleen. Different markers of the same cell did not reappear simultaneously. On the other hand, the same marker (recognized by the monoclonal antibody ED2) reappeared much more rapidly in the liver than in the spleen. The present results in the rat were different from those earlier obtained in the mouse. Red pulp macrophages were the first cells and marginal zone macrophages were the last cells to repopulate the spleen in both rodents after treatment with C12MDP liposomes. However, there was much more overlap in the repopulation kinetics of splenic macrophage subpopulations in the rat, when compared with the mouse.

MeSH terms

  • Acid Phosphatase / metabolism
  • Animals
  • Bone Marrow / drug effects
  • Bone Marrow Cells
  • Cell Count / drug effects
  • Clodronic Acid / administration & dosage
  • Clodronic Acid / pharmacology*
  • Diphosphonates / pharmacology*
  • Female
  • Immunohistochemistry
  • Injections, Intravenous
  • Liposomes
  • Liver / cytology*
  • Liver / drug effects
  • Lung / cytology
  • Lung / drug effects
  • Lymph Nodes / cytology
  • Lymph Nodes / drug effects
  • Lymphoid Tissue / cytology
  • Lymphoid Tissue / drug effects
  • Macrophages / cytology*
  • Macrophages / drug effects
  • Macrophages / enzymology
  • Peritoneal Cavity / cytology
  • Peyer's Patches / cytology
  • Peyer's Patches / drug effects
  • Rats
  • Rats, Inbred Strains
  • Spleen / cytology*
  • Spleen / drug effects
  • Thymus Gland / cytology
  • Thymus Gland / drug effects


  • Diphosphonates
  • Liposomes
  • Clodronic Acid
  • Acid Phosphatase