Basu S, Hodgson G, Zhang H H, Katz M, Quilici C, Dunn A R
Ludwig Institute for Cancer Research, Melbourne Tumor Biology Branch, PO Royal Melbourne Hospital, Victoria 3050, Australia.
Blood. 2000 Jun 15;95(12):3725-33.
Granulocyte colony-stimulating factor (G-CSF) is a glycoprotein believed to play an important role in regulating granulopoiesis both at steady state and during an "emergency" situation. Generation of G-CSF and G-CSF receptor-deficient mice by gene targeting has demonstrated unequivocally the importance of G-CSF in the regulation of baseline granulopoiesis. This study attempted to define the physiologic role of G-CSF during an emergency situation by challenging a cohort of wild-type and G-CSF-deficient mice with Candida albicans. Interestingly, after infection, G-CSF-deficient mice developed an absolute neutrophilia that was observed both in blood and bone marrow. In addition, 3 days after Candida infection increased numbers of granulocyte-macrophage (GM) and macrophage (M) progenitors were observed in the bone marrow of G-CSF-deficient mice. Of the cytokines surveyed, interleukin (IL)-6 levels in serum were elevated; interestingly, levels of IL-6 were higher and more sustained in G-CSF-deficient mice infected with C albicans than similarly infected wild-type mice. Despite the higher levels of serum IL-6, this cytokine is dispensable for the observed neutrophilia because candida-infected IL-6-deficient mice, or mice simultaneously deficient in G-CSF and IL-6, developed neutrophilia. Similarly, mice lacking both G-CSF and GM-CSF developed absolute neutrophilia and had elevated numbers of GM and M progenitors in the bone marrow; thus, G-CSF and GM-CSF are dispensable for promoting the emergency response to candidal infection. (Blood. 2000;95:3725-3733)
粒细胞集落刺激因子（G-CSF）是一种糖蛋白，被认为在稳态和“紧急”情况下调节粒细胞生成中发挥重要作用。通过基因靶向产生G-CSF和G-CSF受体缺陷小鼠已明确证明G-CSF在基线粒细胞生成调节中的重要性。本研究试图通过用白色念珠菌攻击一组野生型和G-CSF缺陷小鼠来确定G-CSF在紧急情况下的生理作用。有趣的是，感染后，G-CSF缺陷小鼠出现了绝对中性粒细胞增多，在血液和骨髓中均观察到。此外，白色念珠菌感染3天后，在G-CSF缺陷小鼠的骨髓中观察到粒细胞-巨噬细胞（GM）和巨噬细胞（M）祖细胞数量增加。在所检测的细胞因子中，血清白细胞介素（IL）-6水平升高；有趣的是，感染白色念珠菌的G-CSF缺陷小鼠的IL-6水平比同样感染的野生型小鼠更高且更持久。尽管血清IL-6水平较高，但这种细胞因子对于观察到的中性粒细胞增多是可有可无的，因为感染念珠菌的IL-6缺陷小鼠或同时缺乏G-CSF和IL-6的小鼠也出现了中性粒细胞增多。同样，同时缺乏G-CSF和GM-CSF的小鼠出现了绝对中性粒细胞增多，骨髓中GM和M祖细胞数量增加；因此，G-CSF和GM-CSF对于促进对念珠菌感染的应急反应是可有可无的。（《血液》。2000年；95:3725 - 3733）
