Involvement of Histamine and RhoA/ROCK in Penicillin Immediate Hypersensitivity Reactions.
Involvement of Histamine and RhoA/ROCK in Penicillin Immediate Hypersensitivity Reactions.
复制标题
组胺和 RhoA/ROCK 参与青霉素速发型超敏反应
DOI：
10.1038/srep33192
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发表时间：
2016-09-13
影响因子：
4.6
通讯作者：
Liang A
中科院分区：
文献类型：
--
作者：
Han J;Yi Y;Li C;Zhang Y;Wang L;Zhao Y;Pan C;Liang A
青霉素速发型超敏反应的机制尚未完全阐明。这些反应通常被认为是由 IgE 介导的，但大多数情况下无法检测到青霉素特异性 IgE。这项研究表明，青霉素能够在模拟青霉素速效过敏反应临床症状的小鼠模型中引起血管通透性过高。首次接触青霉素还会以剂量依赖性方式诱导小鼠耳朵和肺部立即出现水肿和渗出反应。在耳朵的微血管中注意到血管舒张。这些反应不太可能是免疫介导的反应，因为没有产生青霉素特异性 IgE。此外，青霉素治疗直接引起组胺快速释放。青霉素还导致人脐静脉内皮细胞中的 F-肌动蛋白重组，并增加内皮单层的通透性。在青霉素治疗后，在小鼠的耳朵和肺部以及内皮细胞中观察到 RhoA/ROCK 信号通路的激活。抗组胺剂和 ROCK 抑制剂均可减轻小鼠对青霉素的速发型过敏反应。这项研究提出了青霉素速发型超敏反应的新机制，并提出了针对这些反应的潜在预防方法。
The mechanism of penicillin immediate hypersensitivity reactions has not been completely elucidated. These reactions are generally considered to be mediated by IgE, but penicillin-specific IgE could not be detected in most cases. This study demonstrated that penicillin was able to cause vascular hyperpermeability in a mouse model mimicking clinical symptoms of penicillin immediate hypersensitivity reactions. The first exposure to penicillin also induced immediate edema and exudative reactions in ears and lungs of mice in a dose-dependent manner. Vasodilation was noted in microvessels in ears. These reactions were unlikely to be immune-mediated reactions, because no penicillin-specific IgE was produced. Furthermore, penicillin treatment directly elicited rapid histamine release. Penicillin also led to F-actin reorganization in human umbilical vein endothelial cells and increased the permeability of the endothelial monolayer. Activation of the RhoA/ROCK signaling pathway was observed in ears and lungs of mice and in endothelial cells after treatment with penicillin. Both an anti-histamine agent and a ROCK inhibitor attenuated penicillin immediate hypersensitivity reactions in mice. This study presents a novel mechanism of penicillin immediate hypersensitivity reactions and suggests a potential preventive approach against these reactions.
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