Extruded erythroblast nuclei are bound and phagocytosed by a novel macrophage receptor.
Resident bone marrow macrophages (RBMM) play an important role in clearance of nuclei extruded from late-stage erythroblasts (Eb). To investigate the nature of macrophage receptors involved in this process, extruded erythroblast nuclei (EEN) were purified by cultivation of erythroblasts with erythropoietin, followed by density gradient centrifugation. By electron microscopy, the majority of free nuclei had an intact plasma membrane. EEN bound avidly to RBMM in a divalent cation-independent manner at both 4 degrees C and 37 degrees C. The use of specific monoclonal antibodies (MoAbs) and inhibitors showed that this adhesive interaction was not mediated by previously characterized macrophage receptors involved in recognition of either developing hematopoietic cells or apoptotic cells. The EEN receptor was expressed on resident macrophages isolated from murine bone marrow, spleen, lymph node, and peritoneal cavity, but was completely absent from alveolar macrophages. Despite high levels of EEN binding to RBMM, few were phagocytosed even after prolonged culture. Phorbol myristate acetate (PMA) was found to stimulate phagocytosis, suggesting that this is a regulated process. These findings indicate that EEN are recognized by a novel macrophage receptor and that recognition may be triggered during the membrane remodeling that accompanies enucleation.
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L B
LB
Imperial Cancer Research Fund, Oxford University, UK.
Dickson
H
H
Hajibagheri
N
N
Crocker
P R
PR
D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D004900:Erythroblasts / Q000378:metabolism*; D005260:Female; D008264:Macrophages / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010587:Phagocytosis; D011971:Receptors, Immunologic / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D011971:Receptors, Immunologic; D013755:Tetradecanoylphorbol Acetate