Kupffer cell depletion by liposome-delivered drugs: comparative activity of intracellular clodronate, propamidine, and ethylenediaminetetraacetic acid.
Macrophages such as Kupffer cells in the liver are multifunctional cells. They are involved in host defense mechanisms and have a regulatory role in many biomedical processes. Their selective depletion, using liposome-encapsulated drugs, forms a widely accepted approach to studying their functional aspects in vivo. We have compared the Kupffer cell-depleting activities of liposome-encapsulated clodronate, propamidine, and ethylenediaminetetraacetic acid (EDTA) for this purpose. These molecules represent the drug families of bisphosphonates, diamidines (or aromatic polyamidines), and polyaminopolycarboxylic acid-chelating agents, respectively. The Kupffer cell-depleting activity of the liposome-encapsulated antimicrobial drug propamidine exceeded that of clodronate by about a factor of 10. EDTA appeared to be inefficacious for depletion of Kupffer cells in the rat.
Van Rooijen
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Department of Cell Biology and Immunology, Faculty of Medicine, Vrije Universiteit Van der Boechorststraat 7, Amsterdam, The Netherlands.
Sanders
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A
D000818:Animals; D001550:Benzamidines / Q000008:administration & dosage / Q000494:pharmacology*; D002469:Cell Separation; D004002:Clodronic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D004337:Drug Carriers; D004492:Edetic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D007728:Kupffer Cells / Q000166:cytology / Q000187:drug effects*; D008081:Liposomes; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008297:Male; D051381:Rats; D011922:Rats, Mutant Strains
D001550:Benzamidines; D004337:Drug Carriers; D008081:Liposomes; D004002:Clodronic Acid; D004492:Edetic Acid; C005555:propamidine