METHODS FOR ASSESSING SPLENIC MACROPHAGE DEPLETION BY LIPOSOME-ENCAPSULATED CLODRONATE

Small unilamellar vesicles containing clodronate (SUVc) injected intra venously will deplete splenic macrophages and the degree of histologic al depletion can be assessed by determining the clearance and uptake o f monoclonal antibody coated erythrocytes. Splenic Fc dependent cleara nce, assessed in decomplemented animals, provides a more sensitive ind ex of the effects of large multilamellar liposome encapsulated clodron ate (MLVc) and SUVc than does the clearance of complement coated eryth rocytes on macrophage depletion in the spleen. MLVc were more efficien t than SUVc in inducing a reduction in the number of red pulp macropha ges within the spleen. Receptor specific red cell uptake in the spleen could be used as an alternative to histology when assessing splenic m acrophage depletion. Encapsulation of clodronate is crucial to its dep leting effect since the free drug in saline does not change splenic ma crophage number or function.