Measurements of reticuloendothelial system phagocytic activity in the rat after treatment with silica, liposomes, and cyclosporine.
Reticuloendothelial system phagocytosis was evaluated in vivo by the clearance and tissue distribution of 99mTc-albumin millimicrospheres in rats. Administration of i.p. silica 2 days prior to clearance measurement increased the half-life of millimicrospheres 24% compared with control animals (P less than 0.01). Impairment of phagocytic activity was maintained at 5 days to 22% over control values (P less than 0.01). Tissue distribution studies showed that liver uptake was reduced and splenic and pulmonary uptake was increased compared with control. Cyclosporine i.v. increased half-life by 14% 1 hr after administration )P = NS) and half-life returned to control values by 8 hr. Hepatosplenic shift was less marked than after silica treatment. Phospholipid liposomes i.v. produced prompt impairment of millimicrosphere clearance after 1 hr; half-life was prolonged 46% over control values (P less than 0.001 vs. control) and marked radiolabel shift to the spleen and lung was seen. Measurements done 18 hr after a dose of liposomes revealed an increase of 55% over control half-life (P less than 0.001). Liposomes appear to be potent, nontoxic--and, in some cases, reversible agents--for blockade of reticuloendothelial phagocytosis and examination of non-phagocytic reticuloendothelial functions. These results help to explain some of the results obtained in pancreatic islet grafting and suggest that phospholipid liposomes may be useful in this form of transplantation.
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D000818:Animals; D003524:Cyclosporins / Q000008:administration & dosage* / Q000097:blood; D006207:Half-Life; D008081:Liposomes / Q000008:administration & dosage*; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D012157:Mononuclear Phagocyte System / Q000166:cytology / Q000187:drug effects*; D010587:Phagocytosis / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D012822:Silicon Dioxide / Q000008:administration & dosage*; D013154:Spleen / Q000378:metabolism; D013668:Technetium Tc 99m Aggregated Albumin; D013997:Time Factors
D003524:Cyclosporins; D008081:Liposomes; D013668:Technetium Tc 99m Aggregated Albumin; D012822:Silicon Dioxide