Dock2 participates in bone marrow lympho-hematopoiesis
Dock2 participates in bone marrow lympho-hematopoiesis
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DOI：
10.1016/j.bbrc.2007.12.093
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发表时间：
2008-02-29
影响因子：
3.1
通讯作者：
Katayama, Yoshio
中科院分区：
文献类型：
--
作者：
Kikuchi, Tomoko;Kubonishi, Shiro;Katayama, Yoshio
Dock 2作为一种重要的Rac激活因子，对成熟淋巴细胞的趋化性是不可或缺的。然而，Dock 2在未成熟造血细胞中的功能表达尚不清楚。在这项研究中，我们证明了Dock 2广泛表达于骨髓（BM）造血区室，包括造血干/祖细胞（HSC/HPC）部分。Dock 2-/-HPC对CXCL 12的体外趋化性和肌动蛋白聚合反应受损，但CXCL 12对α 4整合素的激活没有改变。体内对HSC的骨髓抑制应激，如连续5-FU给药和连续骨髓移植，在Dock 2-/-小鼠中未显示造血缺陷。移植的Dock 2-/- BM细胞的长期植入在竞争性重建中严重受损。然而，这不是HSC固有的，而是源于Dock 2-/-淋巴前体的竞争缺陷。这些结果表明，Dock 2在骨髓淋巴细胞生成中起重要作用，但对HSC植入和自我更新不利。(C)2007年爱思唯尔公司All rights reserved.
Dock2 has been shown to be indispensable for chemotaxis of mature lymphocytes as a critical Rac activator. However, the functional expression of Dock2 in immature hernatopoietic cells is unclear. In this study, we demonstrate that Dock2 is broadly expressed in bone marrow (BM) hernatopoietic compartment, including hernatopoietic stem/progenitor cell (HSC/HPC) fraction. Response of Dock2-/- HPCs to CXCL12 in chemotaxis and actin polymerization in vitro was impaired, although alpha 4 integrin activation by CXCL12 was not altered. Myelosuppressive stress on HSCs in vivo, such as consecutive 5-FU administration and serial bone marrow transplantation, did not show hernatopoietic defect in Dock2-/- mice. Long-term engraftment of transplanted Dock2-/- BM cells was severely impaired in competitive reconstitution. However, this was not intrinsic to HSCs but originated from the defective competition of Dock2-/- lymphoid precursors. These results suggest that Dock2 plays a significant role in BM lymphopoiesis, but is dispensable for HSC engraftment and self-renewal. (C) 2007 Elsevier Inc. All rights reserved.