Scavenger receptors on liver Kupffer cells mediate the in vivo uptake of oxidatively damaged red blood cells in mice

In vitro studies have shown that damaged red cells and apoptotic cells are efficiently phagocytosed by scavenger receptors from macrophages, even unde r nonopsonizing conditions. Damaged red blood cells are in vivo effectively removed from the blood circulation, but the responsible receptor systems a re largely unknown. We used a murine model in which Cr-51-labeled oxidized red blood cells were injected intravenously, and the cellular uptake sites and the potential involvement of scavenger receptors were analyzed. The dec ay of damaged red cells was rapid (more than 50% removed within 10 minutes after injection), whereas native red cells were not cleared. The main site of uptake of damaged red cells was the liver Kupffer cells, which contained 24% of the injected dose at 10 minutes after injection. The blood decay an d liver uptake were inhibited by typical ligands for scavenger receptors, s uch as polyinosinic acid, liposomes containing phosphatidylserine, oxidized low-density lipoprotein, and fucoidan, but not by polyadenosinic acid or l iposomes without phosphatidylserine. Mice lacking scavenger receptors class A type I and II showed no significant decrease in the ability to take up d amaged red cells from the circulation. We conclude that Kupffer cells are m ainly responsible for the removal of damaged red cells from the blood circu lation, a process mediated by polyinosinic acid- and phosphatidylserine-sen sitive scavenger receptors, different from scavenger receptor class A type I and II. Our data indicate that scavenger receptors, as pattern-recognizin g receptors, play an important role in vivo in the removal of apoptotic, da maged, or other unwanted cells from the blood circulation. (C) 2000 by The American Society of Hematology.