PTX-sensitive signals in bone marrow homing of fetal and adult hematopoietic progenitor cells
PTX-sensitive signals in bone marrow homing of fetal and adult hematopoietic progenitor cells
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DOI：
10.1182/blood-2004-04-1605
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发表时间：
2004-10-15
期刊：
影响因子：
20.3
通讯作者：
Papayannopoulou, T
中科院分区：
文献类型：
--
作者：
Bonig, H;Priestley, GV;Papayannopoulou, T
几个例子表明，在体外迁移能力和骨髓（BM）归巢之间的关系。百日咳毒素（PTX）是蛇形受体相关的抑制性三聚体胍核苷酸结合（Gi）蛋白信号的有效抑制剂。因此，它在体外阻断造血祖细胞迁移，但与预期相反，在先前的研究中未观察到对BM归巢的影响。因此，我们重新检查了PTX对小鼠BM和胎肝（FL）归巢的影响。我们发现，在辐射和非辐射受体中，来自BM或FL的PTX孵育祖细胞（培养物中的集落形成细胞[CFU-Cs]）的BM归巢减少了75%以上，同时外周血中循环CFU-Cs增加。其他研究证实了这种归巢减少的功能意义：PTX处理的细胞不提供辐射保护，并且它们在BM和脾脏中的短期植入急剧减少。此外，几种方法表明，细胞内在的，而不是主机衍生的机制是负责PTX诱导归巢缺陷。总之，我们表明，Gi蛋白信号所需的BM归巢，因此，BM归巢和体外迁移之间的关联提供了一个新的例子。此外，我们的数据表明，造血祖细胞在服从Gi信号传导的行为不偏离成熟白细胞。(C)2004年，美国血液学会。
Several examples suggest a relationship between in vitro migratory capacity and bone marrow (BM) homing. Pertussis toxin (PTX) is a potent inhibitor of serpentine receptor-associated inhibitory trimeric guanidine nucleotide binding (Gi) protein signals. As such, it blocks hematopoietic progenitor cell migration in vitro, but contrary to expectation, no effects on BM homing were observed in previous studies. We therefore re-examined the effect of PTX on homing of murine BM and fetal liver (FL). We found that BM homing of PTX-incubated progenitor cells (colony-forming cells in culture [CFU-Cs]) from BM or FL in irradiated and nonirradiated recipients was reduced by more than 75%, with a concomitant increase in circulating CFU-Cs in peripheral blood. Additional studies confirmed the functional significance of this reduction in homing: PTX-treated cells did not provide radioprotection, and their short-term engraftment in BM and spleen was drastically reduced. Furthermore, several approaches show that cell-intrinsic rather than host-derived mechanisms are responsible for the PTX-induced homing defect. In summary, we show that Gi protein signals are required for BM homing and, as such, provide a new example of the association between BM homing and in vitro migration. Moreover, our data suggest that the behavior of hematopoietic progenitors in obeying Gi signaling does not diverge from that of mature leukocytes. (C) 2004 by The American Society of Hematology.