Enolase-specific cross antibodies induce neutrophilic inflammation in the intestine

Enolase-specific cross antibodies induce neutrophilic inflammation in the intestine
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烯醇酶特异性交叉抗体诱导肠道中性粒细胞炎症

DOI:
10.1002/jlb.3a0620-128r
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发表时间:
2020-08-18
影响因子:
5.5
通讯作者:
Yang, Ping-Chang
Yang, Ping-Chang
中科院分区:
医学3区
文献类型:
--
作者:
Lin, Jianli;Feng, Bai-Sui;Yang, Ping-Chang

文献摘要

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溃疡性结肠炎(UC)的发病机制有待进一步研究。屋尘螨(HDM)与机体免疫性炎症的发病密切相关。本研究旨在探讨烯醇化酶(HDM衍生蛋白之一)特异性交叉抗体在UC样炎症诱导中的作用。采用质谱法对UC患者血清中烯醇化酶特异性免疫球蛋白G(EsIgG)进行鉴定。用EsIgG诱导小鼠结肠黏膜炎症反应。UC患者血清和结肠组织中均检测到EsIg G,且与血和结肠组织中中性粒细胞(PMN)计数呈正相关。EsIg G在小鼠结肠上皮细胞中与构成性烯醇化酶形成免疫复合物,激活补体,诱导上皮细胞凋亡,损害上皮屏障功能,导致小鼠结肠出现类UC炎症。总之,UC患者血清中抗HDM衍生的烯醇化酶和肠上皮细胞衍生的烯醇化酶的抗体水平较高。这些抗体攻击结肠上皮,引起UC样炎症。
The pathogenesis of ulcerative colitis (UC) is to be further investigated. House dust mites (HDM) are highly associated with the pathogenesis of immune inflammation in the body. This study aims to investigate the role of enolase (one of the HDM-derived proteins)-specific cross Abs in the induction of UC-like inflammation. The enolase specific IgG (EsIgG) was identified in UC patients by mass spectrometry. Mice were treated with EsIgG to induce inflammation in the colon mucosa. EsIgG was detected in the serum and the colon tissues of UC patients, which was positively correlated with the polymorphonuclear neutrophil (PMN) counts in the blood and colon tissues of UC patients. EsIgG formed immune complexes with the constitutive enolase in the UC colon epithelium that activated complement, induced epithelial cell apoptosis, compromised epithelial barrier functions, and resulted in UC-like inflammation in the mouse colon. In summary, UC patients have high serum levels of Abs against HDM-derived enolase and intestinal epithelial cell-derived enolase. These Abs attack the colonic epithelium to induce UC-like inflammation.