Defective stromal cell function in a mouse model of infusion-induced bone marrow failure
Defective stromal cell function in a mouse model of infusion-induced bone marrow failure
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DOI：
10.1016/j.exphem.2005.04.008
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发表时间：
2005-08-01
影响因子：
2.6
通讯作者：
Young, NS
中科院分区：
文献类型：
--
作者：
Chen, JC;Brandt, JS;Young, NS
Objective.研究输注诱导的骨髓（BM）衰竭小鼠模型中的BM基质损伤。将5 × 10（6）C57 BL/ 6（B6）淋巴结（LN）细胞输注给亚致死剂量辐照的CByB 6 F1小鼠。在LN输注后第3、7、10和14天取出骨髓细胞，并在α-改良的Eagle培养基中体外培养2-3周。通过全血细胞计数分析外周血，同时通过流式细胞术分析BM淋巴细胞浸润/扩增。将患鼠和对照鼠的骨髓细胞混合并体外培养以检测非特异性间质损伤。供体淋巴细胞在3-7天内浸润宿主BM，并在7 - 10天之间显著扩增，同时发生白细胞减少症、血小板减少症和骨髓发育不全。在B6-LN细胞输注后7、10和14天，来自小鼠的BM细胞在形成基质饲养层方面逐渐缺陷。从受影响的CByB 6 F1小鼠和正常B6小鼠的BM细胞的1：1混合物不能形成有效的基质饲养层，可以支持鹅卵石集落形成，表明受影响的CByB 6 F1小鼠的BM中的淋巴细胞能够破坏正常B6 BM中的基质细胞。在输注诱导的BM衰竭模型中，活化的淋巴细胞作为无辜的旁观者破坏造血细胞和基质细胞。(c)2005年国际实验血液学学会。爱思唯尔公司出版
Objective. To study bone marrow (BM) stromal damage in a mouse model of infusion-induced BM failure.Materials and Methods. Sublethally irradiated CByB6F1 mice were infused with 5 X 10(6) C57BL/ 6 (B6) lymph node (LN) cells. Recipient BM cells were taken at 3, 7, 10, and 14 days following LN infusion and were cultured in vitro in alpha-modified Eagle media for 2-3 weeks. Peripheral blood and was analyzed by complete blood counts while BM lymphocyte infiltration/expansion was analyzed by flow cytometry. Marrow cells from affected and control mice were mixed and cultured in vitro to test nonspecific stromal damage.Results. Donor lymphocytes infiltrated host BM within 3-7 days and expanded significantly between 7 and 10 days, concurrent with the development of leukopenia, thrombocytopenia, and marrow hypoplasia. BM cells from mice at 7, 10, and 14 days after B6-LN cell infusion were progressively defective in forming stromal feeder layers. A 1:1 mixture of BM cells from affected CByB6F1 mice and normal B6 mice failed to form an effective stromal feeder layer that could support cobblestone colony formation, indicating that lymphocytes in the BM of affected CByB6F1 mice were able to damage stromal cells in the normal B6 BM.Conclusion. Activated lymphocytes destroy both hematopoietic and stromal cells as innocent bystanders in the infusion-induced BM failure model. (c) 2005 International Society for Experimental Hematology. Published by Elsevier Inc.