Splenic uptake of RBCs with an elevated cytoplasmic Ca2+-concentration primarily involves marginal zone macrophages and CD207+ dendritic cells
(English)Manuscript (preprint) (Other academic)
Normally senescent red blood cells (RBCs) have a rather fixed life-span after which they are eliminated from the circulation mainly by macrophages in the spleen and liver. However, the normal life-span may be significantly reduced when RBCs are stored under blood bank conditions, which ultimately results in a reduced 24 hour survival after transfusion. Although not completely understood, the damage occurring to some of the stored RBCs is probably multifactorial as stored RBCs shares features of both senescence and suicidal RBC death (eryptosis). One key cellular event associated with eryptosis is an increased intracellular Ca2+-concentration. We found that human RBCs stored for up to 42 days under blood bank conditions contained a small subset of cells with an increased intracellular Ca2+-concentration corresponding to that during eryptosis. Since little is known about the mechanisms mediating uptake and clearance of eryptotic RBCs in vivo, we further investigated this using a murine transfusion model of Ca2+ ionophore-treated RBCs (Ca2+-RBCs). Ca2+-RBCs were mainly trapped by MARCO+ splenic marginal zone macrophages and CD11c+ dendritic cells (DCs) already at 1 hour after transfusion. Among DCs, CD11c+ CD207+ DCs in the marginal zone were particularly efficient in mediating uptake of Ca2+-RBCs. Similar to that found in vitro, CD47 on the Ca2+-RBCs did not affect their clearance in vivo. Thus, RBCs with an increased intracellular Ca2+-concentration accumulates during RBC storage, and in a murine model such RBCs are recognized by splenic macrophages and DCs in ways similar to what has been reported for nucleated apoptotic cells.
Cell and Molecular Biology
Research subject Immunology
IdentifiersURN: urn:nbn:se:umu:diva-103268OAI: oai:DiVA.org:umu-103268DiVA: diva2:812591