Mast cells are required for experimental oral allergen-induced diarrhea
Mast cells are required for experimental oral allergen-induced diarrhea
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DOI：
10.1172/jci200319785
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发表时间：
2003-12-01
影响因子：
15.9
通讯作者：
Rothenberg, ME
中科院分区：
文献类型：
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作者：
Brandt, EB;Strait, RT;Rothenberg, ME
胃肠道过敏性疾病代表了一系列不同的炎性疾病，其发生率和严重程度不断增加。关于这些疾病的一个基本问题是确定负责特定临床表现的特定细胞和介质。考虑到这一点，我们开发了一种小鼠模型，口服过敏原诱导的肠道炎症伴随着强烈的Th 2相关的体液和细胞反应，并专注于过敏性腹泻的免疫发病机制。暴露于反复剂量的胃内OVA的OVA/明矾致敏小鼠诱导的遗传限制性，剂量依赖性，急性腹泻与肠通透性增加，嗜酸性粒细胞增多症，肥大细胞增多症。小鼠出现了有限的全身过敏反应表现，尽管它们出现了明显的肠粘膜肥大细胞脱粒。值得注意的是，涉及肥大细胞耗竭（用抗c-kit mAb）、抗IgE治疗和FcepsilonRI缺陷小鼠的实验表明肥大细胞在介导过敏性腹泻中的关键效应子作用。此外，过敏性腹泻依赖于5-羟色胺和血小板活化因子（PAF）诱导的协同信号，而不是组胺。这些结果表明，口服过敏原诱导的腹泻与实验性Th 2肠道炎症主要是肥大细胞，IgE，血清素和PAF依赖。
Gastrointestinal allergic disorders represent a diverse spectrum of inflammatory diseases that are occurring with increasing incidence and severity. An essential question concerning these disorders is to determine the specific cells and mediators responsible for specific clinical manifestations. With this in mind, we developed a murine model of oral allergen-induced intestinal inflammation accompanied by strong Th2-associated humoral and cellular responses and focused on the immunopathogenesis of allergic diarrhea. Exposure of OVA/alum-sensitized mice to repeated doses of intragastric OVA induced genetically restricted, dose-dependent, acute diarrhea associated with increased intestinal permeability, eosinophilia, and mastocytosis. Mice developed limited systemic manifestations of anaphylaxis, even though they developed marked intestinal mucosal mast cell degranulation. Notably, experiments involving mast cell depletion (with anti-c-kit mAb), anti-IgE treatment, and FcepsilonRI-deficient mice indicated a critical effector role for mast cells in mediating allergic diarrhea. Furthermore, allergic diarrhea was dependent upon synergistic signaling induced by serotonin and platelet-activating factor (PAF), but not histamine. These results demonstrate that oral allergen-induced diarrhea associated with experimental Th2 intestinal inflammation is largely mast cell, IgE, serotonin, and PAF dependent.