circulation by scavenger receptors Liver Kupffer cells rapidly remove red blood cell-derived vesicles from the

Abstract Previous studies have shown that during the life span of red blood cells (RBCs) 20% of hemoglobin is lost by shedding of hemoglobin-containing vesicles. However, the fate of these vesicles is unknown. In order to study this fate we used a rat model, after having established that rat RBCs lose hemoglobin in the same way as human RBCs, and that RBC-derived vesicles are preferentially labeled by Na 251 CrO 4 . Such labeled vesicles were injected into recipient rats. Within five minutes, 80% of the radioactivity was cleared from the circulation with a concomitant uptake by the liver of 55% of the injected dose. After 30 minutes Kupffer cells contained considerable amounts of hemoglobin, and were shown to be responsible for 92% of the liver uptake. Vesicle clearance from the blood as well as liver uptake were significantly inhibited by pre-injection of the scavenger receptor ligands polyinosinic acid and phosphatidylserine. We conclude that in rats Kupffer cells rapidly remove RBC-derived vesicles from the circulation, mainly by scavenger receptors. The same mechanism is likely to be responsible for the elimination of human RBC vesicles, thereby constituting an important pathway for the breakdown of RBCs in man. Corresponding author’s e-mail address: