G-CSF induces the release of the soluble form of LR11, a regulator of myeloid cell mobilization in bone marrow
G-CSF induces the release of the soluble form of LR11, a regulator of myeloid cell mobilization in bone marrow
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G-CSF 诱导可溶形式 LR11 的释放，LR11 是骨髓中骨髓细胞动员的调节剂
DOI：
10.1007/s00277-014-2033-0
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发表时间：
2014
期刊：
影响因子：
3.5
通讯作者：
Bujo H
中科院分区：
文献类型：
--
作者：
Shimizu N;Nakaseko C;Jiang M;Nishii K;Yokote K;Iseki T;Higashi M;Tamaru J;Schneider WJ;Bujo H
粒细胞集落刺激因子（G-CSF）通过一种尚未完全理解的机制诱导白细胞从骨髓（BM）动员到循环中。在这里，我们描述了膜结合受体LR 11在人骨髓细胞中高度表达，并且LR 11的脱落可溶形式（sLR 11）是骨髓细胞迁移的修饰剂。在通过G-CSF治疗动员白细胞的过程中，人和小鼠的循环sLR 11水平短暂升高。此外，在G-CSF治疗后，患者中的sLR 11水平与动员的白细胞数量呈显著正相关。小鼠骨髓细胞中LR 11水平的变化和释放到骨髓液中的sLR 11水平的变化与循环sLR 11水平的变化密切相关。G-CSF剂量依赖性地促进HL-60细胞释放sLR 11，这反过来又加速细胞迁移。最后，sLR 11与肿瘤坏死因子-α（TNF-α）和G-CSF协同作用，增加漂浮细胞（HL-60和U937）与内皮细胞的粘附。我们认为sLR 11是一种新的候选修饰物，可以调节G-CSF介导的血液细胞动员。sLR 11作为G-CSF介导的血液细胞动员的调节组分的鉴定可能有助于进一步改善用于临床应用的血液干细胞收集。
Granulocyte colony-stimulating factor (G-CSF) induces the mobilization of leukocytes from the bone marrow (BM) to the circulation by a yet incompletely understood mechanism. Here, we describe that the membrane-bound receptor LR11 is highly expressed in human myeloid cells and that the shed soluble form of LR11 (sLR11) is a modifier of myeloid cell migration. In the process of leukocyte mobilization by G-CSF treatment, circulating sLR11 levels are transiently elevated in humans and mice. Moreover, following G-CSF treatment, the sLR11 levels in patients show significant positive correlation with the numbers of mobilized leukocytes. The changes of LR11 levels in BM cells and of sLR11 released into the BM fluid of mice correlate tightly with the changes in circulating sLR11 levels. G-CSF dose-dependently enhanced sLR11 release from HL-60 cells, which in turn accelerated cell migration. Finally, cooperatively with tumor necrosis factor-α (TNF-α) and G-CSF, sLR11 increased the attachment of floating cells (HL-60 and U937) to endothelial cells. We propose that sLR11 is a novel candidate modifier of G-CSF-mediated mobilization of hematologic cells. Identification of sLR11 as a regulatory component of G-CSF-mediated hematologic cell mobilization may facilitate further improvement of hematologic stem cell collection for clinical applications.