The c-kit ligand, stem cell factor, can enhance innate immunity through effects on mast cells.
The c-kit ligand, stem cell factor, can enhance innate immunity through effects on mast cells.
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C-KIT配体干细胞因子可以通过对肥大细胞的影响来增强先天免疫力。
DOI：
10.1084/jem.188.12.2343
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发表时间：
1998-12-21
影响因子：
15.3
通讯作者：
Galli, S J
中科院分区：
文献类型：
--
作者：
Maurer, M;Echtenacher, B;Hultner, L;Kollias, G;Mannel, D N;Langley, K E;Galli, S J
肥大细胞被认为是与过敏反应和其他过敏性疾病相关的病理和死亡的重要原因。然而，使用遗传肥大细胞缺陷的WBB6F1-KitW/KitW-v和同源野生型(WBB6F1-+/+)小鼠的研究表明，肥大细胞也可以通过参与对细菌感染的自然免疫反应来促进健康。我们之前曾报道，重复使用c-kit配体干细胞因子(SCF)可以增加正常小鼠体内肥大细胞的数量。体外研究表明，SCF还可以调节肥大细胞效应器功能。我们现在报道，在急性细菌性腹膜炎、盲肠结扎和穿孔(CLP)模型中，SCF治疗可以显著提高正常C57BL/6小鼠的存活率。在重组肥大细胞的WBB6F1-KitW/KitW-v小鼠上的实验表明，SCF处理的这种效应至少部分反映了SCF对肥大细胞的作用。重复应用干细胞因子还可以提高遗传缺乏肿瘤坏死因子-α的小鼠的存活率，这表明干细胞因子治疗提高慢性阻塞性肺疾病后存活率的能力并不仅仅反映干细胞对肥大细胞依赖(或非依赖)产生肿瘤坏死因子-α的影响。这些发现确定c-kit和肥大细胞是增强先天免疫反应的潜在治疗靶点。
Mast cells are thought to contribute significantly to the pathology and mortality associated with anaphylaxis and other allergic disorders. However, studies using genetically mast cell–deficient WBB6F1-KitW/KitW-v and congenic wild-type (WBB6F1-+/+) mice indicate that mast cells can also promote health, by participating in natural immune responses to bacterial infection. We previously reported that repetitive administration of the c-kit ligand, stem cell factor (SCF), can increase mast cell numbers in normal mice in vivo. In vitro studies have indicated that SCF can also modulate mast cell effector function. We now report that treatment with SCF can significantly improve the survival of normal C57BL/6 mice in a model of acute bacterial peritonitis, cecal ligation and puncture (CLP). Experiments in mast cell–reconstituted WBB6F1-KitW/KitW-v mice indicate that this effect of SCF treatment reflects, at least in part, the actions of SCF on mast cells. Repetitive administration of SCF also can enhance survival in mice that genetically lack tumor necrosis factor (TNF)-α, demonstrating that the ability of SCF treatment to improve survival after CLP does not solely reflect effects of SCF on mast cell– dependent (or –independent) production of TNF-α. These findings identify c-kit and mast cells as potential therapeutic targets for enhancing innate immune responses.