Rho 和 Rac，但不是 ROCK，对于人嗜酸性粒细胞相关核糖核酸酶和鼠嗜酸性粒细胞相关核糖核酸酶的分泌是必需的。
Rho and Rac, but not ROCK, are required for secretion of human and mouse eosinophil-associated RNases.
机构信息
Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Division of Allergy and Inflammation, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
出版信息
Clin Exp Allergy. 2019 Feb;49(2):190-198. doi: 10.1111/cea.13292. Epub 2018 Nov 19.
BACKGROUND
Eosinophil-associated RNases (EARs) are stored preformed in eosinophil cytoplasmic secretory granules and have a key role in eosinophil effector functions in host defence and inflammatory disorders. However, the secretion mechanisms of EARs are poorly understood.
OBJECTIVE
Our study aimed to understand the involvement of cytoskeleton machinery in EAR secretion.
METHODS
Fresh human and mouse eosinophils were stimulated with CCL11, and the secretion of enzymatically active EARs was detected using an RNase activity assay. The involvement of cytoskeletal elements or microtubules was probed using specific inhibitors.
RESULTS
We found that dynamic polymerization of microtubules and cytoskeletal elements, such as Rho and Rac, is required for chemokine-mediated EAR secretion from human and mouse eosinophils. However, inhibition of ROCK (Rho-associated protein kinase) increased EAR secretion in human and mouse eosinophils even in the absence of chemokine stimulation, suggesting ROCK negatively regulates EAR secretion.
CONCLUSIONS
Collectively, these data suggest a cytoskeleton-dependent mechanism of EAR secretion from eosinophils, findings that are pertinent to host defence, allergy and other eosinophil-associated diseases.
背景
嗜酸性粒细胞相关核糖核酸酶（EARs）以前体形式储存在嗜酸性粒细胞胞质分泌颗粒中，在宿主防御和炎症性疾病中的嗜酸性粒细胞效应功能中起关键作用。然而，EARs 的分泌机制还知之甚少。
目的
我们的研究旨在了解细胞骨架机制在 EAR 分泌中的作用。
方法
用 CCL11 刺激新鲜的人源和鼠源嗜酸性粒细胞，并用核糖核酸酶活性测定法检测具有酶活性的 EARs 的分泌情况。使用特定的抑制剂来探测细胞骨架成分或微管的参与情况。
结果
我们发现微管和细胞骨架成分（如 Rho 和 Rac）的动态聚合对于趋化因子介导的人源和鼠源嗜酸性粒细胞中的 EAR 分泌是必需的。然而，即使在没有趋化因子刺激的情况下，抑制 ROCK（Rho 相关蛋白激酶）也会增加人源和鼠源嗜酸性粒细胞中的 EAR 分泌，这表明 ROCK 负调控 EAR 分泌。
结论
综上所述，这些数据表明嗜酸性粒细胞 EAR 分泌是一种依赖细胞骨架的机制，这对于宿主防御、过敏和其他与嗜酸性粒细胞相关的疾病具有重要意义。
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