A SULFATED CHITIN, SCM-CHITIN-III, INHIBITS THE CLEARANCE OF HUMAN ERYTHROCYTES FROM THE BLOOD-CIRCULATION IN ERYTHROCYTE-TRANSFUSED SCID MICE

Recently, we have developed a SCID mouse model in which circulating re d blood cells (RBC) are entirely substituted with RBCs from other anim als like bovine (Be) or human (Hu). The relatively short life time, es pecially of Hu-RBCs, in the SCID mouse, however, is a major obstacle i n this model. The present study was performed to examine whether a low -toxic sulfated chitin, carboxymethyl chitin III (SCM-chitin III), whi ch has heparin-like structures in the molecule (heparinoid), could inh ibit the Hu-RBC clearance in RBC-transfused SCID mice. When Hu-RBCs we re transfused simultaneously with SCM-chitin III, their life time in t he blood circulation was prolonged significantly. Sulfated chitosan (S -chitosan) showed only a weak decelerating activity on the clearance o f Hu-RBCs. Carboxymethyl chitin (CM-chitin), which was used as an unsu lfated control compound, had no effect on the Hu-RBC clearance. Anothe r sulfated polysaccharide, dextran sulfate, though this showed some ad verse effects, such as anti-coagulant and anti-platelet aggregation, a lso exhibited a potent decelerating activity on Hu-RBC clearance. Clea rance deceleration by these sulfated polysaccharides was primarily att ributable to the inhibition of RBC uptake by cultured macrophages.