DEK, a nuclear protein, is chemotactic for hematopoietic stem/progenitor cells acting through CXCR2 and Gαi signaling.
DEK, a nuclear protein, is chemotactic for hematopoietic stem/progenitor cells acting through CXCR2 and Gαi signaling.
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DOI：
10.1002/jlb.3ab1120-740r
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发表时间：
2022-09
影响因子：
5.5
通讯作者：
Markovitz, David M.
中科院分区：
文献类型：
--
作者：
Capitano, Maegan L.;Sammour, Yasser;Ropa, James;Legendre, Maureen;Mor-Vaknin, Nirit;Markovitz, David M.
已知很少有细胞因子/生长调节蛋白是造血干细胞（HSC）和祖细胞（HPC）的化学引诱物;基质细胞衍生因子1α（SDF 1 α/CXCL 12）是已知最有效的此类蛋白。DEK是一种具有造血细胞因子样活性的核DNA结合染色质蛋白，是一种吸引成熟免疫细胞的趋化因子。进行Transwell迁移测定以测试DEK是否充当HSC/HPC的趋化剂。DEK诱导谱系阴性（Lin-）Sca-1+ c-Kit+（LSK）骨髓（BM）细胞、HSC和HPC的剂量和时间依赖性定向迁移。生物板试验表明，DEK的活性是趋化性（定向），而不是化学动力学（随机迁移），在性质上。DEK和SDF 1 α竞争HSC/HPC趋化性。用中和抗体阻断CXCR 2或用百日咳毒素预处理抑制Gαi蛋白信号传导可抑制LSK细胞向DEK迁移。因此，DEK是一种新型和罕见的HSC/HPC趋化剂，以直接或间接的CXCR 2和Gαi蛋白偶联信号传导依赖性方式起作用。核蛋白DEK以CXCR 2和Gαi蛋白偶联信号传导依赖性方式作为造血干细胞和祖细胞的趋化因子。
Few cytokines/growth modulating proteins are known to be chemoattractants for hematopoietic stem (HSC) and progenitor cells (HPC); stromal cell‐derived factor 1α (SDF1α/CXCL12) being the most potent known such protein. DEK, a nuclear DNA‐binding chromatin protein with hematopoietic cytokine‐like activity, is a chemotactic factor attracting mature immune cells. Transwell migration assays were performed to test whether DEK serves as a chemotactic agent for HSC/HPC. DEK induced dose‐ and time‐dependent directed migration of lineage negative (Lin–) Sca‐1+ c‐Kit+ (LSK) bone marrow (BM) cells, HSCs and HPCs. Checkerboard assays demonstrated that DEK's activity was chemotactic (directed), not chemokinetic (random migration), in nature. DEK and SDF1α compete for HSC/HPC chemotaxis. Blocking CXCR2 with neutralizing antibodies or inhibiting Gαi protein signaling with Pertussis toxin pretreatment inhibited migration of LSK cells toward DEK. Thus, DEK is a novel and rare chemotactic agent for HSC/HPC acting in a direct or indirect CXCR2 and Gαi protein‐coupled signaling‐dependent manner. The nuclear protein DEK acts as a chemotactic factor for hematopoietic stem and progenitor cells in a CXCR2‐ and Gαi protein‐coupled signaling‐dependent manner.