Aging human erythrocytes. Differential sensitivity of young and old erythrocytes to hemolysis induced by peroxide in the presence of thyroxine.
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We have previously developed an in vivo experimental system for a bovine hemoprotozoan parasite, in which SCID mice were periodically transfused with bovine red blood cells (Bo-RBCs), followed by infection with the parasite. The SCID mice prepared by the original method, however, had both mouse and bovine RBCs in the circulation, and their proportion always fluctuated significantly. In the present study, we aimed to deplete the mouse RBCs circulating in SCID mice and, thereby, to create SCID mice having complete Bo-RBC substitution. An anti-erythropoietin rabbit serum, an anti-mouse RBC rabbit serum and 23 monoclonal anti-mouse RBC rat antibodies were prepared for this purpose. They were examined, after administration into SCID mice, for their ability to decrease hematocrit value and also for any other adverse effect. A monoclonal antibody, clone 2E11, was found to have potent ability to induce clearance of the mouse RBCs in SCID mice without causing toxic effects. SCID mice receiving this antibody together with periodic transfusion of Bo-RBCs had their circulating RBCs completely substituted with Bo-RBCs. Infection of Bo-RBC-SCID mice with bovine hemoprotozoan parasites demonstrated that elimination of the mouse RBCs from Bo-RBC-SCID mice resulted in augmentation of parasite growth.
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Recently, we have developed a SCID mouse model in which circulating red blood cells (RBC) are entirely substituted with RBCs from other animals like bovine (Bo) or human (Hu). The relatively short life time, especially of Hu-RBCs, in the SCID mouse, however, is a major obstacle in this model. The present study was performed to examine whether a low-toxic sulfated chitin, carboxymethyl chitin III (SCM-chitin III), which has heparin-like structures in the molecule (heparinoid), could inhibit the Hu-RBC clearance in RBC-transfused SCID mice. When Hu-RBCs were transfused simultaneously with SCM-chitin III, their life time in the blood circulation was prolonged significantly. Sulfated chitosan (S-chitosan) showed only a weak decelerating activity on the clearance of Hu-RBCs. Carboxymethyl chitin (CM-chitin), which was used as an unsulfated control compound, had no effect on the Hu-RBC clearance. Another sulfated polysaccharide, dextran sulfate, though this showed some adverse effects, such as anti-coagulant and anti-platelet aggregation, also exhibited a potent decelerating activity on Hu-RBC clearance. Clearance deceleration by these sulfated polysaccharides was primarily attributable to the inhibition of RBC uptake by cultured macrophages.
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