A sulfated chitin, SCM-chitin III, inhibits the clearance of human erythrocytes from the blood circulation in erythrocyte-transfused SCID mice

Abstract

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.