BACKGROUND IgG can mediate murine and human systemic anaphylaxis (SA). The roles of mast cells (MCs) and histamine in IgG-mediated anaphylaxis are controversial for mice and have not been studied in vivo for humans. We are now investigating these issues. METHODS Actively or passively sensitized wild-type and immune-deficient mice were induced to develop anaphylaxis by intravenous antigen challenge. Anaphylaxis was characterized by evaluating hypothermia, hypomobility, histamine, and MC protease responses. RESULTS In contrast to our previous results with protein-immunized mice from a conventional colony, IgG-mediated passive SA in our specific pathogen-free colony mice depended considerably on histamine produced by connective tissue MCs (CTMCs) in response to FcγRIII crosslinking. This was found for C57BL/6 and young male and female BALB/c mice, including BALB/c mice newly arrived from 3 vendors. IgG-mediated anaphylaxis was less histamine dependent in old than young mice. Although both mucosal MC (MMC) and CTMC responses were severely depleted in c-kit-deficient mice, MMC responses depended considerably more than CTMC responses on c-kit for maintenance. In immunologically naive mice, FcγRIII crosslinking strongly activated a subset of CTMCs but had little ability to activate MMCs. In vivo LPS + poly I:C treatment decreased histamine dependence of IgG-mediated anaphylaxis, while a strong TH2 immune response increased FcγRIII crosslinking-induced MMC activation. IgG-mediated activation of human MCs in reconstituted immunodeficient mice induced histamine-dependent anaphylaxis. CONCLUSION IgG-dependent SA can be mediated largely by histamine released by mouse CTMCs and human MCs; histamine dependence is influenced by mouse age, sex, and immune and infectious history, as well as the anaphylaxis model studied.

中文翻译：

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肥大细胞组胺分泌在 IgG 介导的系统性过敏反应中的重要性。


背景 IgG 可介导小鼠和人全身性过敏反应 （SA）。肥大细胞 （MCs） 和组胺在 IgG 介导的过敏反应中的作用对小鼠存在争议，尚未对人类进行体内研究。我们现在正在调查这些问题。方法 通过静脉注射抗原攻击诱导主动或被动致敏野生型和免疫缺陷小鼠发生过敏反应。过敏反应的特征是评估体温过低、活动不足、组胺和 MC 蛋白酶反应。结果与我们之前对来自常规集落的蛋白质免疫小鼠的结果相比，我们特异性无病原体集落小鼠中 IgG 介导的被动 SA 在很大程度上依赖于结缔组织 MC （CTMC） 响应 FcγRIII 交联产生的组胺。这在 C57BL/6 和年轻的雄性和雌性 BALB/c 小鼠中发现，包括从 3 家供应商新到的 BALB/c 小鼠。IgG 介导的过敏反应在老年小鼠中比年轻小鼠对组胺的依赖性更低。尽管 c-kit 缺陷小鼠的粘膜 MC （MMC） 和 CTMC 反应都严重耗尽，但 MMC 反应比 CTMC 反应对 c-kit 的维持依赖程度要大得多。在免疫学初治小鼠中，FcγRIII 交联强烈激活 CTMC 的一个子集，但激活 MMC 的能力很小。体内 LPS + poly I：C 处理降低了 IgG 介导的过敏反应的组胺依赖性，而强烈的 TH2 免疫反应增加了 FcγRIII 交联诱导的 MMC 激活。IgG 介导的重组免疫缺陷小鼠中人 MC 的激活诱导组胺依赖性过敏反应。 结论 IgG 依赖性 SA 主要由小鼠 CTMC 和人 MC 释放的组胺介导;组胺依赖受小鼠年龄、性别、免疫和感染史以及所研究的过敏反应模型的影响。