Methods for assessing splenic macrophage depletion by liposome encapsulated clodronate.
Small unilamellar vesicles containing clodronate (SUVc) injected intravenously will deplete splenic macrophages and the degree of histological depletion can be assessed by determining the clearance and uptake of monoclonal antibody coated erythrocytes. Splenic Fc dependent clearance, assessed in decomplemented animals, provides a more sensitive index of the effects of large multilamellar liposome encapsulated clodronate (MLVc) and SUVc than does the clearance of complement coated erythrocytes on macrophage depletion in the spleen. MLVc were more efficient than SUVc in inducing a reduction in the number of red pulp macrophages within the spleen. Receptor specific red cell uptake in the spleen could be used as an alternative to histology when assessing splenic macrophage depletion. Encapsulation of clodronate is crucial to its depleting effect since the free drug in saline does not change splenic macrophage number or function.
Camilleri
J P
JP
Department of Rheumatology, University Hospital of Wales, Heath Park, Cardiff, UK.
Williams
A S
AS
Amos
N
N
Douglas-Jones
A G
AG
Love
W G
WG
Williams
B D
BD
D000818:Animals; D002452:Cell Count; D004002:Clodronic Acid / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D003179:Complement C3b / Q000502:physiology; D003165:Complement System Proteins / Q000502:physiology; D004912:Erythrocytes / Q000276:immunology; D007249:Inflammation / Q000473:pathology*; D008081:Liposomes / Q000008:administration & dosage; D008264:Macrophages / Q000276:immunology / Q000473:pathology*; D008297:Male; D051381:Rats; D011961:Receptors, Fc / Q000502:physiology; D013154:Spleen / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*
D008081:Liposomes; D011961:Receptors, Fc; D004002:Clodronic Acid; D003179:Complement C3b; D003165:Complement System Proteins