EXTRUDED ERYTHROBLAST NUCLEI ARE BOUND AND PHAGOCYTOSED BY A NOVEL MACROPHAGE RECEPTOR

Resident bone marrow macrophages (RBMM) play an important role in clea rance of nuclei extruded from late-stage erythroblasts (Eb). To invest igate the nature of macrophage receptors involved in this process, ext ruded erythroblast nuclei (EEN) were purified by cultivation of erythr oblasts with erythropoietin, followed by density gradient centrifugati on. By electron microscopy, the majority of free nuclei had an intact plasma membrane. EEN bound avidly to RBMM in a divalent cation-indepen dent 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 r eceptors involved in recognition of either developing hematopoietic ce lls or apoptotic cells. The EEN receptor was expressed on resident mac rophages isolated from murine bone marrow, spleen, lymph node, and per itoneal cavity, but was completely absent from alveolar macrophages. D espite 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. T hese findings indicate that EEN are recognized by a novel macrophage r eceptor and that recognition may be triggered during the membrane remo deling that accompanies enucleation. (C) 1995 by The American Society of Hematology.