Respiratory burst of neutrophils is not required for stem cell mobilization in mice.
Respiratory burst of neutrophils is not required for stem cell mobilization in mice.
复制标题
小鼠干细胞动员不需要中性粒细胞的呼吸爆发。
DOI：
10.1046/j.1365-2141.2000.02374.x
复制
发表时间：
2000
影响因子：
6.5
通讯作者：
Mauch,PM
中科院分区：
文献类型：
--
作者：
vanOs,R;Robinson,SN;Drukteinis,D;Sheridan,TM;Mauch,PM
已经表明，成熟的中性粒细胞可能在导致干细胞从骨髓流出到外周血的级联事件中发挥重要作用。为了进一步研究成熟的中性粒细胞和活性氧中间体（ROI）的作用，已知参与中性粒细胞的信号转导，我们使用呼吸爆发缺陷的小鼠，从而产生ROI，研究干细胞动员中这种激活途径的参与。患有慢性肉芽肿病（CGD）的B6小鼠在第1天接受环磷酰胺（200 mg/kg），在第3-6天接受粒细胞集落刺激因子（G-CSF）（250 µg/kg/d）或单次给予白细胞介素8（IL-8; 30 µg/小鼠）作为动员方案。 在第7天，将血液和骨髓中干细胞和祖细胞的数量与对照B6动物（具有完整的呼吸爆发）进行比较。测定第7天（CAFC-7）和第28天（CAFC-28）的白色血细胞计数、骨髓细胞结构以及粒细胞-巨噬细胞集落形成细胞（GM-CFC）和鹅卵石区域形成细胞（CAFC）的频率。在环磷酰胺和G-CSF（CY + G）后，两种小鼠品系均显示CAFC-7和CFU-GM大量动员至血液中。 正常小鼠每毫升血液中的祖细胞增加了1905倍，而CGD小鼠的血液祖细胞增加了264倍。IL-8还诱导两种小鼠品系的动员。除了祖细胞外，在正常小鼠和CGD小鼠中，在第35天测量为CAFC-28和CAFC的原始干细胞也通过两种动员方案动员。总之，呼吸爆发和随后的信号转导途径似乎不需要动员干细胞。因此，嗜中性粒细胞不参与干细胞动员，或者嗜中性粒细胞内必须存在导致激活干细胞从骨髓排出的因子释放的其他信号传导途径。
It has been suggested that mature neutrophils may play an essential role in the cascade of events leading to egress of stem cells from the bone marrow to the peripheral blood. To investigate further the role of mature neutrophils and of reactive oxygen intermediates (ROIs), known to be involved in the signal transduction of neutrophils, we used mice deficient in respiratory burst, and thus the production of ROIs, to study the involvement of this activation pathway in stem cell mobilization. B6 mice with chronic granulomatous disease (CGD) received either cyclophosphamide (200 mg/kg) on day 1 and granulocyte colony‐stimulating factor (G‐CSF) (250 µg/kg/d) on days 3–6 or a single dose of interleukin 8 (IL‐8; 30 µg/mouse) as a mobilization regimen. On day 7, the number of stem and progenitor cells in blood and bone marrow was compared with control B6 animals (with intact respiratory burst). White blood cell counts, bone marrow cellularity and the frequency of granulocyte–macrophage colony‐forming cells (GM‐CFC), and cobblestone area‐forming cells (CAFC) on days 7 (CAFC‐7) and 28 (CAFC‐28) were determined. After cyclophosphamide and G‐CSF (CY + G), both mouse strains showed considerable mobilization of CAFC‐7 and CFU‐GM to the blood. Normal mice showed up to a 1905‐fold increase in progenitors per ml blood, whereas CGD mice showed up to a 264‐fold increase in blood progenitors. IL‐8 also induced mobilization in both mouse strains. In addition to progenitors, primitive stem cells measured as CAFC‐28 and as CAFC at day 35 were also mobilized by both mobilization protocols in normal as well as in CGD mice. In conclusion, respiratory burst and the subsequent signal transduction pathway do not appear to be required for mobilization of stem cells. Accordingly, neutrophils either are not involved in stem cell mobilization or other signalling pathways within neutrophils must exist that lead to the release of factors which activate stem cell egress from the bone marrow.