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 s tudies, using probes to evaluate hepatic Fc and C3b uptake, showed a c lose correlation between the inhibition of receptor-mediated uptake an d the depletion of hepatic macrophages. Twenty milligrams of clodronat e encapsulated within SUVc produced greater than or equal to 90% inhib ition of uptake and clearance of Fc- and C3b-coated erythrocytes and a comparable reduction of hepatic macrophage numbers. Inhibition of mac rophage receptor-mediated uptake of these erythroctyes was closely rel ated to the reduction in macrophage numbers. Repopulation of macrophag es within the liver took place over 2 weeks. At 1 week after depletion , although repopulation was taking place, receptor-mediated function r emained suppressed. In a preliminary experiment, treatment of rats wit h adjuvant arthritis with 20 mg clodronate encapsulated in SUV suppres sed the inflammation and reversed the course of the disease, while tre atment with 20 mg free clodronate in saline or 20 mg clodronate in mul tilamellar vesicles (MLVc) did not.