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Liposome mediated affection of monocytes
I Huitinga1, J G Damoiseaux, N van Rooijen
1Department of Cell Biology, Medical Faculty, Vrije Universiteit, Amsterdam, The Netherlands.
Abstract:
Dichloromethylene diphosphonate (Cl2MDP) enclosed in liposomes, when injected intravenously, selectively eliminates all phagocytizing macrophages that are in direct contact with the blood circulation of the spleen and the liver. We examined whether Cl2MDP containing liposomes affect, in addition, rat monocytes and bone marrow macrophage precursors (BMMP's). In addition to Phosphatidylcholine-Cholesterol liposomes (PC liposomes), we also used mannosylated PC liposomes (PCMAN liposomes), which are reported to bind more efficiently to macrophages. Monocytes appeared to be affected 24 h after injections of 2 ml of Cl2MDP containing PC as well as PCMAN liposomes. In addition, almost no macrophages could be detected in one week cultures of blood leukocytes isolated from these animals; cultures from control animals contained +/- 50% macrophages. Bone marrow macrophage precursors did not appear to be affected.
Insights
Liposomes containing dichloromethylene diphosphonate (Cl2MDP) eliminate circulating macrophages. This study found Cl2MDP liposomes affect rat monocytes but not bone marrow macrophage precursors.
Area of Science:
- Immunology
- Pharmacology
- Cell Biology
Background:
- Dichloromethylene diphosphonate (Cl2MDP) encapsulated in liposomes targets phagocytic macrophages in the spleen and liver.
- Liposomes, particularly mannosylated ones (PCMAN), enhance drug delivery to macrophages.
Purpose of the Study:
- To investigate the effects of Cl2MDP-containing liposomes on rat monocytes and bone marrow macrophage precursors (BMMP's).
- To compare the efficacy of standard Phosphatidylcholine-Cholesterol (PC) liposomes versus PCMAN liposomes in targeting these cells.
Main Methods:
- Intravenous injection of Cl2MDP-loaded PC and PCMAN liposomes into rats.
- Isolation of blood leukocytes and bone marrow cells at 24 hours and one week post-injection.
- Culturing of isolated cells to assess macrophage presence and differentiation.
Main Results:
- Cl2MDP liposomes (both PC and PCMAN) significantly reduced the number of monocytes in rats 24 hours after injection.
- Macrophage populations derived from blood leukocytes of treated rats were nearly absent in cultures.
- Bone marrow macrophage precursors (BMMP's) remained unaffected by the Cl2MDP liposome treatment.
Conclusions:
- Cl2MDP-loaded liposomes effectively deplete circulating monocytes and their macrophage progeny.
- PCMAN liposomes show similar efficacy to PC liposomes in affecting monocytes.
- The study highlights the potential of Cl2MDP liposomes for modulating monocyte/macrophage populations, sparing bone marrow precursors.