Phagocytosis of liquid-stored red blood cells in vitro requires serum and macrophage scavenger receptors
(English)Manuscript (preprint) (Other academic)
BACKGROUND: Red blood cells (RBCs) undergo structural and metabolic changes with prolonged storage, which ultimately may decrease their survival after transfusion. Although the storage-induced damage to RBCs has been rather well described biochemically, little is known about the mechanisms underlying the recognition and rapid clearance of the damaged cells by macrophages.STUDY DESIGN AND METHODS: We here used a murine model for cold (+4°C) RBC storage and transfusion. Phagocytosis of human or murine RBCs, liquid stored for 6-8 weeks or 10-14 days respectively, was investigated in murine peritoneal macrophages.RESULTS: The effects of storage on murine RBCs resembled that described for stored human RBCs with regard to decreased adenosine triphosphate (ATP) levels, accumulation of microparticles during storage, and RBC recovery kinetics after transfusion. Under serum-free conditions, phagocytosis of stored human or murine RBCs was reduced by 70-75%, as compared with that in the presence of heat-inactivated fetal calf serum (FCS). Human serum promoted phagocytosis of stored human RBCs similar to that seen with FCS. By blocking macrophage class A scavenger receptors with fucoidan or dextran sulphate, phagocytosis of human or murine RBCs was reduced by more than 90%. Phagocytosis of stored human RBCs was also sensitive to inhibition by the phosphatidylinositol 3 kinase-inhibitor LY294002, the ERK1/2-inhibitor PD98059, or the p38 MAPK-inhibitor SB203580.CONCLUSIONS: RBCs damaged during liquid storage may be recognized by macrophage class A scavenger receptors and serum-dependent mechanisms. This species-independent recognition mechanism may help to further understand the rapid clearance of stored RBCs shortly after transfusion.
Cell and Molecular Biology
Research subject transfusionsmedicin
IdentifiersURN: urn:nbn:se:umu:diva-103266OAI: oai:DiVA.org:umu-103266DiVA: diva2:812587