A novel role of complement in mobilization: Immunodeficient mice are poor granulocyte-colony stimulating factor mobilizers because they lack complement-activating immunoglobulins
A novel role of complement in mobilization: Immunodeficient mice are poor granulocyte-colony stimulating factor mobilizers because they lack complement-activating immunoglobulins
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DOI：
10.1634/stemcells.2007-0525
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发表时间：
2007-01-01
期刊：
影响因子：
5.2
通讯作者：
Ratajczak, Mariusz Z.
中科院分区：
文献类型：
--
作者：
Reca, Ryan;Cramer, Daniel;Ratajczak, Mariusz Z.
补体(C)和先天免疫是造血干/祖细胞(HSPC)动员的重要调节因子，但尚未得到充分认识。我们报道：(A)在粒细胞集落刺激因子(G-CSF)诱导的经典免疫球蛋白(Ig)依赖途径的动员过程中，骨髓(BM)中的C被激活；(B)C3裂解片段增加了HSPC对基质衍生因子-1梯度的反应性。由于患有严重联合免疫缺陷(SCID)的患者活动能力差，我们推测这可能与这些患者缺乏C活化Ig有直接联系。在目前的研究中，为了更好地阐明C激活在HSPC动员中的作用，我们用G-CSF或酵母多糖动员缺乏Ig的小鼠(RAG2、SCID和JH)，这两种化合物分别通过经典的Ig依赖途径和替代的Ig非依赖途径激活C。此外，我们还评估了C5缺乏的动物的动员情况。通过检测外周血中粒细胞、巨噬细胞和白细胞的集落形成单位数来评价动员效果。我们发现：(A)在RAG2、SCID和JH小鼠中，G-CSF诱导的动员严重减少；(B)在输注纯化的野生型Ig后，受损的G-CSF诱导的动员得到恢复；以及(C)在C5缺乏的小鼠中，动员严重减少。这些数据提供了强有力的证据，证明C系统在HSPC的动员中起着关键作用，HSPC从骨髓中流出是作为免疫反应的一部分。
Complement ( C) and innate immunity emerge as important and underappreciated modulators of mobilization of hematopoietic stem/progenitor cells (HSPC). We reported that ( a) C becomes activated in bone marrow ( BM) during granulocyte-colony-stimulating factor (G-CSF)-induced mobilization by the classic immunoglobulin (Ig)-dependent pathway and that (b) C3 cleavage fragments increase the responsiveness of HSPC to a stromal derived factor-1 gradient. Since patients suffering from severe combined immunodeficiency ( SCID) mobilize poorly, we hypothesized that this could be directly linked to the lack of C activating Ig in these patients. In the current study to better elucidate the role of C activation in HSPC mobilization, we mobilized mice that lack Ig (RAG2, SCID, and Jh) by G-CSF or zymosan, compounds that activate C by the classic Ig-dependent and the alternative Ig-independent pathways, respectively. In addition, we evaluated mobilization in C5-deficient animals. Mobilization was evaluated by measuring the number of colony-forming unit-granulocyte macrophage and leukocytes circulating in peripheral blood. We found that ( a) G-CSF- but not zymosan-induced mobilization was severely reduced in RAG2, SCID, and Jh mice; (b) impaired G-CSF- induced mobilization was restored after infusion of purified wild-type Ig; and ( c) mobilization was severely reduced in C5-deficient mice. These data provide strong evidence that the C system plays a pivotal role in mobilization of HSPC and that egress of HSPC from BM occurs as part of an immune response.