Red blood cells with elevated cytoplasmic Ca2+ are primarily taken up by splenic marginal zone macrophages and CD207+dendritic cells
2016 (English)In: Transfusion, ISSN 0041-1132, E-ISSN 1537-2995, Vol. 56, no 7, 1834-1844 p.Article in journal (Refereed) Published
BACKGROUND: The normal red blood cell (RBC) life span may be significantly reduced when RBCs are stored under blood bank conditions, resulting in a reduced 24-hour survival after transfusion. The damage of stored RBCs is probably multifactorial as stored RBCs share features of both senescence and suicidal RBC death (eryptosis). Since an increased intracellular Ca2+ concentration ([Ca2+](i)) is one key feature of eryptosis, we here investigated if stored human RBCs had increased [Ca2+](i) and the mechanisms behind uptake of such RBCs in a murine model.
STUDY DESIGN AND METHODS: The intracellular Ca2+ content of RBCs was determined using the Ca2+ probe Fluo-3 and flow cytometry. In vivo uptake of Ca2+ ionophore-treated murine RBCs (Ca2+-RBCs) was investigated in recipient mice, using flow cytometry and immunohistochemical analysis.
RESULTS: A small fraction of human RBCs accumulated [Ca2+](i) during storage for up to 42 days under blood bank conditions. In a murine model, where fresh or Ca2+-RBCs were transfused, Ca2+-RBCs were mainly trapped by MARCO+ splenic marginal zone macrophages and CD11c+ CD207+ dendritic cells (DCs) within 1 hour after transfusion. In marked contrast, freshly transfused RBCs aging normally in circulation were cleared much slower and preferentially by F4/80+ red pulp macrophages. CD47 on the Ca2+-RBCs did not affect their clearance by splenic phagocytic cells.
CONCLUSIONS: A small fraction of RBCs accumulate [Ca2+](i) during 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.
Place, publisher, year, edition, pages
2016. Vol. 56, no 7, 1834-1844 p.
IdentifiersURN: urn:nbn:se:umu:diva-125594DOI: 10.1111/trf.13612ISI: 000380362100025PubMedID: 27095001OAI: oai:DiVA.org:umu-125594DiVA: diva2:973967