Imamura Rie, Miyamoto Toshihiro, Yoshimoto Goichi, Kamezaki Kenjiro, Ishikawa Fumihiko, Henzan Hideho, Kato Koji, Takase Ken, Numata Akihiko, Nagafuji Koji, Okamura Takashi, Sata Michio, Harada Mine, Inaba Shoichi
Blood Transfusion Service, Kyushu University Hospital, Fukuoka, Japan.
J Immunol. 2005 Aug 15;175(4):2647-54. doi: 10.4049/jimmunol.175.4.2647.
Hemopoietic stem and progenitor cells ordinarily residing within bone marrow are released into the circulation following G-CSF administration. Such mobilization has a great clinical impact on hemopoietic stem cell transplantation. Underlying mechanisms are incompletely understood, but may involve G-CSF-induced modulation of chemokines, adhesion molecules, and proteolytic enzymes. We studied G-CSF-induced mobilization of CD34+ CD10+ CD19- Lin- and CD34+ CD10+ CD19+ Lin- cells (early B and pro-B cells, respectively). These mobilized lymphoid populations could differentiate only into B/NK cells or B cells equivalent to their marrow counterparts. Mobilized lymphoid progenitors expressed lymphoid- but not myeloid-related genes including the G-CSF receptor gene, and displayed the same pattern of Ig rearrangement status as their bone marrow counterparts. Decreased expression of VLA-4 and CXCR-4 on mobilized lymphoid progenitors as well as multipotent and myeloid progenitors indicated lineage-independent involvement of these molecules in G-CSF-induced mobilization. The results suggest that by acting through multiple trans-acting signals, G-CSF can mobilize not only myeloid-committed populations but a variety of resident marrow cell populations including lymphoid progenitors.
通常存在于骨髓中的造血干细胞和祖细胞在给予粒细胞集落刺激因子(G-CSF)后会释放到循环中。这种动员对造血干细胞移植具有重大临床影响。其潜在机制尚未完全了解,但可能涉及G-CSF诱导的趋化因子、黏附分子和蛋白水解酶的调节。我们研究了G-CSF诱导的CD34+CD10+CD19-Lin-和CD34+CD10+CD19+Lin-细胞(分别为早期B细胞和前B细胞)的动员情况。这些动员的淋巴细胞群体只能分化为B/NK细胞或与其骨髓对应细胞相当的B细胞。动员的淋巴细胞祖细胞表达淋巴细胞相关而非髓系相关基因,包括G-CSF受体基因,并显示出与其骨髓对应细胞相同的Ig重排状态模式。动员的淋巴细胞祖细胞以及多能和髓系祖细胞上VLA-4和CXCR-4表达的降低表明这些分子在G-CSF诱导的动员中存在不依赖谱系的参与。结果表明,通过多种反式作用信号,G-CSF不仅可以动员髓系定向群体,还可以动员包括淋巴细胞祖细胞在内的各种驻留骨髓细胞群体。