Department of Oral Anatomy and Developmental Biology, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
Cell Immunol. 2011;271(1):197-204. doi: 10.1016/j.cellimm.2011.06.025. Epub 2011 Jul 5.
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.
我们之前的研究表明，注射含氮双膦酸盐（NBP）会导致红细胞生成部位从骨髓（BM）转移到脾脏。这是由于支持红细胞生成的 BM 驻留巨噬细胞耗竭所致。在这项研究中，我们检查了 NBP 治疗诱导的脾切除小鼠的骨髓外造血，重点研究了肝造血。NBP 处理的小鼠没有出现贫血或促红细胞生成素产生的显著变化，而巨核细胞生成和红细胞生成在肝脏中持续观察到。红系细胞岛在窦状腔中被检测到。Kupffer 细胞在 NBP 处理后表达 VCAM-1，这是红系细胞分化的重要因素。Cl(2)MBP-脂质体处理耗尽了红系细胞岛，并通过集落形成测定减少了肝脏中的造血细胞数量。总之，这些结果表明，Kupffer 细胞支持红细胞生成，在肝脏中充当基质细胞，并且在紧急情况下可能充当造血前体细胞的龛位。
