A new protective role for S100A9 in regulation of neutrophil recruitment during invasive pneumococcal pneumonia
A new protective role for S100A9 in regulation of neutrophil recruitment during invasive pneumococcal pneumonia
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DOI：
10.1096/fj.13-247460
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发表时间：
2014-08-01
期刊：
影响因子：
4.8
通讯作者：
Hogg, Nancy
中科院分区：
文献类型：
--
作者：
De Filippo, Katia;Neill, Daniel R.;Hogg, Nancy
S100 A8/A9异源二聚体在骨髓细胞，特别是中性粒细胞中大量表达，但其作用机制仅部分确定。在这项研究中，我们研究了S100 A8/A9参与宿主对肺炎链球菌感染的反应，使用在骨髓细胞中缺乏异二聚体表达的S100 a9（-/-）小鼠。鼻内感染肺炎球菌的S100 a9（-/-）小鼠迅速死亡，48小时后死亡率为80%，而大多数野生型小鼠恢复。在这段时间内，S100 a9（-/-）小鼠的循环和肺部募集的中性粒细胞平均减少了6倍。S100 a9（-/-）肺的Taqman分析显示，与中性粒细胞募集相关的5种细胞因子和趋化因子的优势亚群的产生减少。最大的差异是细胞因子粒细胞集落刺激因子（G-CSF）导致骨髓释放中性粒细胞进入循环（48小时差异1900倍）。用G-CSF治疗S100 a9（-/-）小鼠通过增强循环中性粒细胞和中性粒细胞向感染肺的募集，通过减少肺炎球菌集落形成单位，以及通过升高趋化因子CXCL 1、细胞因子IL-6和内源性G-CSF蛋白，逆转了它们对感染的易感性增加。因此，S100 A9可能与其伴侣S100 A8一起，通过增加循环中性粒细胞主要调节G-CSF的产生，在宿主对肺炎球菌感染的反应中做出了重大贡献。De Filippo，K.，Neill，D. R.，Mathies，M.，Bangert，M.，麦克尼尔，Kadioglu，A.，Hogg，N. S100 A9在侵袭性肺炎球菌肺炎中性粒细胞募集调节中的新保护作用
The S100A8/A9 heterodimer is abundantly expressed by myeloid cells, especially neutrophils, but its mechanism of action is only partially determined. In this study we investigated S100A8/A9 involvement in the host response to Streptococcus pneumoniae infection making use of S100a9(-/-) mice that lack heterodimer expression in myeloid cells. S100a9(-/-) mice that were infected intranasally with pneumococci rapidly succumbed, with 80% mortality after 48 h, whereas the majority of wild-type mice recovered. Over this time period, S100a9(-/-) mice displayed an average 6-fold reduction in circulating and lung-recruited neutrophils. Taqman analysis of S100a9(-/-) lungs revealed decreased production of a dominant subset of 5 cytokines and chemokines associated with neutrophil recruitment. The greatest differential was with the cytokine granulocyte colony-stimulating factor (G-CSF) that causes bone marrow release of neutrophils into the circulation (1900-fold difference at 48 h). Treating S100a9(-/-) mice with G-CSF reversed their increased susceptibility to infection by enhancing both circulating neutrophils and neutrophil recruitment into infected lungs, by reducing pneumococcal colony forming units, and by elevation of chemokine CXCL1, cytokine IL-6, and endogenous G-CSF proteins. Thus S100A9, potentially with its partner S100A8, makes a major contribution in the host response to pneumococcal infection by increasing circulating neutrophils principally regulation of G-CSF production.-De Filippo, K., Neill, D. R., Mathies, M., Bangert, M., McNeill, E., Kadioglu, A., Hogg, N. A new protective role for S100A9 in regulation of neutrophil recruitment during invasive pneumococcal pneumonia.