Mast Cell-Derived TNF Can Exacerbate Mortality during Severe Bacterial Infections in C57BL/6-KitW-sh/W-sh Mice
Mast Cell-Derived TNF Can Exacerbate Mortality during Severe Bacterial Infections in C57BL/6-KitW-sh/W-sh Mice
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DOI：
10.2353/ajpath.2010.090342
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发表时间：
2010-02-01
影响因子：
6
通讯作者：
Galli, Stephen J.
中科院分区：
文献类型：
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作者：
Piliponsky, Adrian M.;Chen, Ching-Cheng;Galli, Stephen J.
我们使用肥大细胞移植的遗传性肥大细胞缺陷的C57 BL/6-Kit（W-sh/W-sh）小鼠来研究肥大细胞和肥大细胞衍生的肿瘤坏死因子在两种严重细菌感染模型中的作用。在这些小鼠中，我们证实了来自肥大细胞缺陷型WBB 6 F（1）-Kit（W/W-v）小鼠研究的结果，表明肥大细胞可以促进中度盲肠结扎穿孔（CLP）小鼠的存活。然而，我们发现肥大细胞在这种情况下的有益作用可以独立于肥大细胞源性肿瘤坏死因子而发生。相比之下，使用肥大细胞移植的C57 BL/6-Kit（W-sh/W-sh）小鼠，我们发现肥大细胞衍生的肿瘤坏死因子可以增加严重CLP期间的死亡率，也可以增强细菌生长，并在腹膜内接种鼠伤寒沙门氏菌后加速死亡。在WBB 6 F（1）-Kit（W-sh/W-sh）小鼠中，肥大细胞在中度重度CLP中提高了存活率，但在重度CLP中观察到的存活率没有显著变化。因此，我们在三种遗传性肥大细胞缺陷小鼠中的发现支持了以下假设：（包括小鼠品系背景、导致肥大细胞缺陷的突变的性质以及感染的类型和严重性），肥大细胞在细菌感染期间对存活可能没有可检测的作用或具有相反的作用，例如，在中度重度CLP期间促进存活与低死亡率相关，但在C57 BL/6-Kit（W-sh/W-sh）小鼠中，在重度CLP或感染S.鼠伤寒。(Am J Pathol 2010，176：926-938; DOI：10.2353/ajpath.2010.090342）
We used mast cell-engrafted genetically mast cell-deficient C57BL/6-Kit(W-sh/W-sh) mice to investigate the roles of mast cells and mast cell-derived tumor necrosis factor in two models of severe bacterial infection. In these mice, we confirmed findings derived from studies of mast cell-deficient WBB6F(1)-Kit(W/W-v) mice indicating that mast cells can promote survival in cecal ligation and puncture (CLP) of moderate severity. However, we found that the beneficial role of mast cells in this setting can occur independently of mast cell-derived tumor necrosis factor. By contrast, using mast cell-engrafted C57BL/6-Kit(W-sh/W-sh) mice, we found that mast cell-derived tumor necrosis factor can increase mortality during severe CLP and can also enhance bacterial growth and hasten death after intraperitoneal inoculation of Salmonella typhimurium. in WBB6F(1)-Kit(W-sh/W-sh) mice, mast cells enhanced survival during moderately severe CLP but did not significantly change the survival observed in severe CLP. Our findings in three types of genetically mast cell-deficient mice thus support the hypothesis that, depending on the circumstances (including mouse strain background, the nature of the mutation resulting in a mast cell deficiency, and type and severity of infection), mast cells can have either no detectable effect or opposite effects on survival during bacterial infections, eg, promoting survival during moderately severe CLP associated with low mortality but, in C57BL/6-Kit(W-sh/W-sh) mice, increasing mortality during severe CLP or infection with S. typhimurium. (Am J Pathol 2010, 176:926-938; DOI: 10.2353/ajpath.2010.090342)