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Red blood cells with elevated cytoplasmic Ca 2+ are primarily taken up by splenic marginal zone macrophages and CD207+ dendritic cells
Author(s) -
Larsson Anders,
Hult Andreas,
Nilsson Anna,
Olsson Mattias,
Oldenborg PerArne
Publication year - 2016
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/trf.13612
Subject(s) - spleen , flow cytometry , phagocytosis , red pulp , biology , mononuclear phagocyte system , intracellular , microbiology and biotechnology , andrology , red blood cell , phosphatidylserine , chemistry , immunology , biochemistry , medicine , phospholipid , membrane
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 Ca 2+ concentration ([Ca 2+ ] i ) is one key feature of eryptosis, we here investigated if stored human RBCs had increased [Ca 2+ ] i and the mechanisms behind uptake of such RBCs in a murine model. STUDY DESIGN AND METHODS The intracellular Ca 2+ content of RBCs was determined using the Ca 2+ probe Fluo‐3 and flow cytometry. In vivo uptake of Ca 2+ ionophore–treated murine RBCs (Ca 2+ ‐RBCs) was investigated in recipient mice, using flow cytometry and immunohistochemical analysis. RESULTS A small fraction of human RBCs accumulated [Ca 2+ ] i during storage for up to 42 days under blood bank conditions. In a murine model, where fresh or Ca 2+ ‐RBCs were transfused, Ca 2+ ‐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 Ca 2+ ‐RBCs did not affect their clearance by splenic phagocytic cells. CONCLUSIONS A small fraction of RBCs accumulate [Ca 2+ ] 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.