title: MerTK-mediated engulfment of pyrenocytes by central macrophages in erythroblastic islands.
abstract: Definitive erythropoiesis takes place at erythroblastic islands, where erythroblasts proliferate and differentiate in association with central macrophages. At the final stage of erythropoiesis, pyrenocytes (nuclei surrounded by plasma membranes) are excluded from erythroblasts, expose phosphatidylserine (PtdSer), and are engulfed by the macrophages in a PtdSer-dependent manner. However, the molecular mechanism(s) involved in the engulfment of pyrenocytes are incompletely understood. Here, we constructed an in vitro assay system for the enucleation and engulfment of pyrenocytes using a methylcellulose-based culture. As reported previously, erythroblasts were bound to macrophages via interactions between integrin-α4β1 on erythroblasts and Vcam1 on macrophages. After enucleation, the resulting pyrenocytes exhibited a reduced affinity for Vcam1 that correlated with the presence of inactive integrin-α4β1 complexes. The pyrenocytes were then engulfed by the macrophages via a MerTK-protein S-dependent mechanism. Protein S appeared to function as a bridge between the pyrenocytes and macrophages by binding to PtdSer on the pyrenocytes and MerTK on the macrophages. Normally, NIH3T3 cells do not engulf pyrenocytes, but when they were transformed with MerTK, they efficiently engulfed pyrenocytes in the presence of protein S. These results suggest that macrophages use similar mechanisms to engulf both pyrenocytes and apoptotic cells.
authors.affiliation: Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, and.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Toda
authors.affiliation: Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, and.
authors.forename: Katsumori
authors.initials: K
authors.lastname: Segawa
authors.affiliation: Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, and Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Kyoto, Japan.
authors.forename: Shigekazu
authors.initials: S
authors.lastname: Nagata
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D004900:Erythroblasts / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D004910:Erythrocyte Membrane / Q000378:metabolism; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism*; D004920:Erythropoiesis; D057809:HEK293 Cells; D006801:Humans; D039041:Integrin alpha4beta1 / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D041681:NIH 3T3 Cells; D010587:Phagocytosis; D011485:Protein Binding; D017293:Protein S / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D012156:Reticulocytes / Q000166:cytology / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D000076202:c-Mer Tyrosine Kinase
chemical_list: D039041:Integrin alpha4beta1; D017293:Protein S; D011518:Proto-Oncogene Proteins; D019010:Vascular Cell Adhesion Molecule-1; C490767:Mertk protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D000076202:c-Mer Tyrosine Kinase