The effect of free and liposome-encapsulated clodronate on the hepatic mononuclear phagocyte system in the rat.
Clodronate, encapsulated within small unilamellar vesicles (SUVc) will deplete hepatic macrophages after intravenous injection. Functional studies, using probes to evaluate hepatic Fc and C3b uptake, showed a close correlation between the inhibition of receptor-mediated uptake and the depletion of hepatic macrophages. Twenty milligrams of clodronate encapsulated within SUVc produced > or = 90% inhibition of uptake and clearance of Fc- and C3b-coated erythrocytes and a comparable reduction of hepatic macrophage numbers. Inhibition of macrophage receptor-mediated uptake of these erythrocytes was closely related to the reduction in macrophage numbers. Repopulation of macrophages within the liver took place over 2 weeks. At 1 week after depletion, although repopulation was taking place, receptor-mediated function remained suppressed. In a preliminary experiment, treatment of rats with adjuvant arthritis with 20 mg clodronate encapsulated in SUV suppressed the inflammation and reversed the course of the disease, while treatment with 20 mg free clodronate in saline or 20 mg clodronate in multilamellar vesicles (MLVc) did not.
Department of Rheumatology, University Hospital of Wales, Cardiff, UK.
J P
JP
Camilleri
A S
AS
Williams
N
N
Amos
A G
AG
Douglas-Jones
W G
WG
Love
B D
BD
Williams
D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy; D004002:Clodronic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D004337:Drug Carriers; D004546:Elapid Venoms / Q000494:pharmacology; D004912:Erythrocytes / Q000378:metabolism; D007124:Immunoenzyme Techniques; D008081:Liposomes; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects*; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D017463:Receptors, Complement 3b / Q000378:metabolism; D011961:Receptors, Fc / Q000378:metabolism
D004337:Drug Carriers; D004546:Elapid Venoms; D008081:Liposomes; D017463:Receptors, Complement 3b; D011961:Receptors, Fc; C016310:cobra venom factor; D004002:Clodronic Acid