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Liposome mediated depletion of macrophages: mechanism of action, preparation of liposomes and applications

Liposome mediated depletion of macrophages: mechanism of action, preparation of liposomes and applications

Journal of Immunological Methods 174(1-2): 83-93

Selective depletion of macrophages from tissues in vivo can be used to investigate whether these cells are playing a role in defined biological processes. This question is particularly relevant to various host defense mechanisms. We have developed a macrophage 'suicide' technique, using the liposome mediated intracellular delivery of dichloromethylene-bisphosphonate (Cl-2MBP or clodronate). The method is specific with respect to phagocytic cells of the mononuclear phagocyte system (MPS) for the following reasons: (1) The natural fate of liposomes is phagocytosis. (2) Once ingested by macrophages, the phospholipid bilayers of the liposomes are disrupted under the influence of lysosomal phospholipases. (3) Cl-2MBP intracellularly released in this way does not easily escape from the cell by crossing the cell membranes. (4) Cl-2MBP released in the circulation from dead macrophages or by leakage from liposomes, will not easily enter non-phagocytic cells and has an extremely short half life in the circulation and body fluids. In the present review, the preparation of Cl-2MBP-liposomes has, been described in detail. Furthermore, the mechanism of action of the new approach and its applicabilities are discussed.

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Accession: 008961473

Download citation: RISBibTeXText

PMID: 8083541

DOI: 10.1016/0022-1759(94)90012-4

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