Abstract:
Bone marrow adipose tissue (BMAT) is hypothesized to serve as an expandable/contractible fat depot which functions, in part, to minimize energy requirements for sustaining optimal hematopoiesis. We investigated whether BMAT is required for immune reconstitution following injury. Male wild type (WBB6F1, WT) and BMAT-deficient WBB6F1/J-KitW/KitW-v/J (KitW/W-v) mice were lethally irradiated. Irradiation was followed by adoptive transfer of 1000 purified WT hematopoietic stem cells (HSCs). The extent of immune reconstitution in blood, bone marrow, and lymph nodes in the irradiated mice was determined using HSCs from green fluorescent protein (GFP)-expressing mice. We also evaluated skeletal response to treatment. Detection of GFP-positive B and T cells in peripheral blood at 4 and 9 weeks following adoptive transfer and in bone marrow and lymph nodes following necropsy revealed excellent immune reconstitution in both WT and BMAT-deficient mice. Adipocytes were numerous in the distal femur of WT mice but absent or rare in KitW/W-v mice. Bone parameters, including length, mass, density, bone volume, microarchitecture, and turnover balance, exhibited few differences between WT and BMAT-deficient mice. The minimal differences suggest that BMAT is not required for reconstitution of the immune system following lethal radiation and is not a major contributor to the skeletal phenotypes of kit signaling-deficient mice.
摘要:
骨髓脂肪组织(BMAT)被认为是一种可扩张/可收缩的脂肪储库,在某种程度上,以最小化维持最佳造血功能的能量需求。我们调查了损伤后免疫重建是否需要BMAT。对雄性野生型(WBB6F1,WT)和BMAT缺陷型WBB6F1/J-KitW/KitW-v/J(KitW/W-v)小鼠进行致死性照射。照射之后是1000个纯化的WT造血干细胞(HSC)的过继转移。血液中免疫重建的程度,骨髓,使用来自绿色荧光蛋白(GFP)表达小鼠的HSC测定照射小鼠中的淋巴结。我们还评估了骨骼对治疗的反应。在过继转移后4周和9周时,在外周血中以及尸检后在骨髓和淋巴结中检测到GFP阳性B和T细胞,在WT和BMAT缺陷小鼠中均显示出出色的免疫重建。WT小鼠的股骨远端脂肪细胞很多,但在KitW/W-v小鼠中不存在或很少见。骨参数,包括长度,质量,密度,骨体积,微体系结构,和营业额余额,WT和BMAT缺陷小鼠之间几乎没有差异。最小差异表明,致命辐射后免疫系统的重建不需要BMAT,并且不是试剂盒信号传导缺陷型小鼠骨骼表型的主要贡献者。