In vivo visualization of eosinophil secretion in eosinophilic granulomatosis with polyangiitis: An ultrastructural study
In vivo visualization of eosinophil secretion in eosinophilic granulomatosis with polyangiitis: An ultrastructural study
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DOI：
10.1016/j.alit.2022.02.009
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发表时间：
2022-07-01
影响因子：
6.8
通讯作者：
Katsuno, Masahisa
中科院分区：
文献类型：
--
作者：
Koike, Haruki;Nishi, Ryoji;Katsuno, Masahisa
背景资料：虽然嗜酸性肉芽肿伴多血管炎（EGPA）被认为是属于抗中性粒细胞胞浆抗体（ANCA）相关血管炎的单一疾病实体，但一些研究表明，除了与ANCA相关的机制外，与嗜酸性粒细胞相关的机制在组织损伤中起着至关重要的作用。尽管如此，嗜酸性粒细胞相关病变的形态学基础尚未完全阐明。方法：我们调查了从18例EGPA患者的腓肠神经活检标本的电子显微镜结果，通过专注于嗜酸性粒细胞的行为，特别是分泌的模式。结果：嗜酸性粒细胞往往位于靠近内皮细胞的神经外膜小血管内腔内的网站。观察到嗜酸性粒细胞与内皮细胞的附着，特别是在相邻内皮细胞之间的连接处，并且这些嗜酸性粒细胞中的一些似乎从血管腔中逃逸到血管外内膜中。此外，我们观察到嗜酸性粒细胞脱粒通过零碎脱粒和细胞溶解。在血管内和血管外室中均发现了脱颗粒嗜酸性粒细胞。一些小血管似乎被许多嗜酸性粒细胞闭塞，血小板附着的嗜酸性粒细胞也被观察到，这表明凝血病发生在EGPA.Conclusions：血管外和血管内嗜酸性粒细胞可以诱导组织损伤无关的经典坏死性血管炎与ANCA在EGPA患者。进一步的研究是必要的，以阐明诱导这些细微结构变化的分子基础，这将有助于基于嗜酸性粒细胞相关疾病的特定机制的靶向治疗的发展。Copyright（c）2022，Japanese Society of Allergology.制作和托管由Elsevier B. V.这是一个开放获取的文章在CC BY-NC-ND许可证（http：//creativecommons.org/licenses/by-nc-nd/4.0/）。
Background: Although eosinophilic granulomatosis with polyangiitis (EGPA) has been considered as a single disease entity belonging to anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, several studies have suggested that in addition to the mechanisms associated with ANCA, those associated with eosinophils play a vital role in tissue damage. Nevertheless, the morphological bases underlying eosinophil-associated lesions have not been completely elucidated.Methods: We investigated the electron microscopic findings of sural nerve biopsy specimens obtained from 18 patients with EGPA by focusing on the behavior of eosinophils, particularly the mode of secretion.Results: Eosinophils tended to be located at sites close to endothelial cells within the lumina of epineurial small vessels. Attachment of eosinophils to endothelial cells was observed, particularly at the junction between neighboring endothelial cells, and some of these eosinophils appeared to escape from the vascular lumen to migrate into the extravascular interstitium. Furthermore, we observed eosinophil degranulation via piecemeal degranulation and cytolysis. Degranulating eosinophils were identified in both intravascular and extravascular compartments. Some of the small vessels appeared to be occluded by numerous eosinophils, and eosinophils attached by platelets were also observed, suggesting that coagulopathy occurs in EGPA.Conclusions: Both extravascular and intravascular eosinophils can induce tissue damage unrelated to classical necrotizing vasculitis associated with ANCA in patients with EGPA. Further research is necessary to elucidate the molecular basis of the induction of these fine structural changes, which will contribute to the development of targeted therapies based on specific mechanisms of eosinophil-related diseases.Copyright (c) 2022, Japanese Society of Allergology. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).