Annexin-2 is a regulator of stromal cell-derived factor-1/CXCL12 function in the hematopoietic stem cell endosteal niche
Annexin-2 is a regulator of stromal cell-derived factor-1/CXCL12 function in the hematopoietic stem cell endosteal niche
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DOI：
10.1016/j.exphem.2010.11.007
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发表时间：
2011-02-01
影响因子：
2.6
通讯作者：
Taichman, Russell S.
中科院分区：
文献类型：
--
作者：
Jung, Younghun;Shiozawa, Yusuke;Taichman, Russell S.
Objective.此前，我们报道了膜联蛋白-2（anxa 2）在造血干细胞（HSC）定位于骨内膜/成骨细胞骨髓龛中发挥重要作用。本研究探讨了膜联蛋白-2在向HSC呈递基质细胞衍生因子-1（或CXCL 12）中的作用。竞争性长期骨髓移植试验用于确定在膜联蛋白-2缺陷动物中HSC植入是否改变。集落形成细胞测定，CXCL 12酶联免疫吸附试验，实时逆转录聚合酶链反应分析被用来确定干细胞或祖细胞动员粒细胞集落刺激因子。采用免疫组织化学、免疫沉淀、结合试验和趋化试验来确定膜联蛋白2是否与CXCL 12相关。降解试验也用于确定膜联蛋白-2和CXCL 12是否相互保护免受蛋白水解降解。anxa 2（-/-）动物骨髓中的HSC较少，并且anxa 2（-/-）动物中的HSC表达较少的CXCR 4和CXCR 7，表明细胞内在缺陷。野生型骨髓移植到anxa 2（-/-）动物的研究表明，在anxa 2（-/-）动物的细胞外源性缺陷。CXCL 12直接与膜联蛋白-2结合，这种相互作用促进CXCL 12向HSC呈递。然而，CXCL 12与膜联蛋白2的结合并不能保护CXCL 12在粒细胞集落刺激因子动员干细胞或祖细胞后免受蛋白水解切割。这些结果表明，膜联蛋白-2作为CXCL 12的锚，以帮助HSC定位到龛。(C)2011 ISEH -血液学和干细胞学会。爱思唯尔公司出版
Objective. Previously, we reported that annexin-2 (anxa2) plays an important role in hematopoietic stem cell (HSC) localization to the endosteal/osteoblastic marrow niche. This study explored the role that annexin-2 plays in presenting stromal cell-derived factor - 1 (or CXCL12) to HSCs.Materials and Methods. Competitive long-term bone marrow transplant assays were used to determine if HSC engraftment is altered in annexin-2 - deficient animals. Colony-forming cell assays, CXCL12 enzyme-linked immunosorbent assay, and real-time reverse transcription polymerase chain reaction analyses were used to determine stem or progenitor cell mobilization by granulocyte colony-stimulating factor. Immunohistochemistry, immunoprecipitation, binding assays, and chemotactic assays were employed to determine if annexin-2 is associated with CXCL12. Degradation assays were also used to determine if annexin-2 and CXCL12 protect each other from proteolytic degradation.Results. Anxa2(-/-) animals had fewer HSCs in their marrow, and the HSCs in anxa2(-/-) animals express less CXCR4 and CXCR7, suggesting a cell intrinsic defect. Transplantation studies of wild-type marrow into anxa2(-/-) animals demonstrated a cell-extrinsic defect in the anxa2(-/-) animals. CXCL12 binds directly to annexin-2, and this interaction facilitates presentation of CXCL12 to HSCs. Yet the binding of CXCL12 to annexin-2 did not protect CXCL12 from proteolytic cleavage after stem or progenitor cell mobilization by granulocyte colony-stimulating factor.Conclusions. These results suggest that annexin-2 serves as an anchor for CXCL12 to help in the localization of HSCs to the niche. (C) 2011 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.