title: Kupffer cells support extramedullary erythropoiesis induced by nitrogen-containing bisphosphonate in splenectomized mice.
abstract: Our previous study indicated that injecting nitrogen-containing bisphosphonate (NBP) induced the site of erythropoiesis to shift from the bone marrow (BM) to the spleen. This was due to the depletion of BM-resident macrophages, which support erythropoiesis. In this study, we examined NBP treatment-induced extramedullary hematopoiesis in splenectomized mice, focusing on hepatic hematopoiesis. NBP-treated mice did not display anemia or significant change in erythropoietin production, while megakaryopoiesis and erythropoiesis were constantly observed in the liver. Erythroblastic islands were detected in the sinusoidal lumen. Kupffer cells expressed VCAM-1 following NBP treatment, which is an important factor for erythroblast differentiation. Cl(2)MBP-liposome treatment depleted the erythroblastic islands, and decreased the number of hematopoietic cells in the liver, as determined by colony forming assays. Together, these results indicate that Kupffer cells support erythropoiesis, acting as stromal cells in the liver, and that they might act as a niche for hematopoietic precursor cells in an emergency.
authors.affiliation: Department of Oral Anatomy and Developmental Biology, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
authors.forename: Hirotada
authors.initials: H
authors.lastname: Otsuka
authors.forename: Hideki
authors.initials: H
authors.lastname: Yagi
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Endo
authors.forename: Naoko
authors.initials: N
authors.lastname: Nonaka
authors.forename: Masanori
authors.initials: M
authors.lastname: Nakamura
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000235:genetics; D000943:Antigens, Differentiation / Q000378:metabolism; D001789:Blood Group Antigens / Q000378:metabolism; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism; D004164:Diphosphonates / Q000494:pharmacology*; D004900:Erythroblasts / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D004920:Erythropoiesis / Q000187:drug effects*; D004921:Erythropoietin / Q000097:blood; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006400:Hematocrit; D007150:Immunohistochemistry; D007728:Kupffer Cells / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D017467:Receptors, Erythropoietin / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013156:Splenectomy; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: C514497:4-amino-1-hydroxybutylidene-1,1-diphosphonate; D018952:Antigens, CD34; D000943:Antigens, Differentiation; D001789:Blood Group Antigens; D004164:Diphosphonates; D017467:Receptors, Erythropoietin; C489122:TER-119 antigen, mouse; D019010:Vascular Cell Adhesion Molecule-1; C036763:monocyte-macrophage differentiation antigen; D004921:Erythropoietin