S100A8/A9 是释放中性粒细胞胞外陷阱并诱导中性粒细胞活化的标志物,Cells

当前位置： X-MOL 学术 › Cells › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

S100A8/A9 是释放中性粒细胞胞外陷阱并诱导中性粒细胞活化的标志物
Cells ( IF 5.1 ) Pub Date : 2022-01-11 , DOI: 10.3390/cells11020236
Evelien G G Sprenkeler _{1,

2} , Judith Zandstra _{2,

3} , Nadine D van Kleef _{1,

3} , Ines Goetschalckx ₁ , Bibian Verstegen _{1,

3} , Cathelijn E M Aarts ₁ , Hans Janssen ₄ , Anton T J Tool ₁ , Gerard van Mierlo ₃ , Robin van Bruggen ₁ , Ilse Jongerius _{2,

3} , Taco W Kuijpers _{1,

2}

Affiliation

中性粒细胞是循环中最丰富的先天免疫细胞，它们是第一个被招募到感染或炎症部位的细胞。中性粒细胞中几乎一半的细胞内蛋白质含量由 S100A8 和 S100A9 组成，尽管关于它们的实际定位存在争议。一旦释放到细胞外，这些蛋白质被认为充当损伤相关分子模式 (DAMP)，尽管它们的作用机制尚不清楚。这些 S100 蛋白主要形成异二聚体（S100A8/A9，也称为钙卫蛋白），这种异源复合物被认为是几种炎症性疾病的有用生物标志物。我们观察到 S100A8/A9 高度存在于中性粒细胞的细胞质部分中，并且不是颗粒内容物的一部分。此外，我们发现 S100A8/A9 不是与颗粒物质同时释放，而是在中性粒细胞胞外陷阱 (NETs) 形成时释放。因此，缺乏佛波醇 12-肉豆蔻酸酯 13-乙酸 (PMA) 诱导的 NETosis 的慢性肉芽肿病患者的中性粒细胞在 PMA 刺激后不会释放 S100A8/A9。此外，我们从中性粒细胞的细胞质部分中纯化了 S100A8/A9，发现 S100A8/A9 可以诱导中性粒细胞活化，包括粘附和 CD11b 上调，表明这种 DAMP 可能会放大中性粒细胞活化。在 PMA 刺激下没有释放 S100A8/A9。此外，我们从中性粒细胞的细胞质部分中纯化了 S100A8/A9，发现 S100A8/A9 可以诱导中性粒细胞活化，包括粘附和 CD11b 上调，表明这种 DAMP 可能会放大中性粒细胞活化。在 PMA 刺激下没有释放 S100A8/A9。此外，我们从中性粒细胞的细胞质部分中纯化了 S100A8/A9，发现 S100A8/A9 可以诱导中性粒细胞活化，包括粘附和 CD11b 上调，表明这种 DAMP 可能会放大中性粒细胞活化。

"点击查看英文标题和摘要"

S100A8/A9 Is a Marker for the Release of Neutrophil Extracellular Traps and Induces Neutrophil Activation

Neutrophils are the most abundant innate immune cells in the circulation and they are the first cells recruited to sites of infection or inflammation. Almost half of the intracellular protein content in neutrophils consists of S100A8 and S100A9, though there has been controversy about their actual localization. Once released extracellularly, these proteins are thought to act as damage-associated molecular patterns (DAMPs), though their mechanism of action is not well understood. These S100 proteins mainly form heterodimers (S100A8/A9, also known as calprotectin) and this heterocomplex is recognized as a useful biomarker for several inflammatory diseases. We observed that S100A8/A9 is highly present in the cytoplasmic fraction of neutrophils and is not part of the granule content. Furthermore, we found that S100A8/A9 was not released in parallel with granular content but upon the formation of neutrophil extracellular traps (NETs). Accordingly, neutrophils of patients with chronic granulomatous disease, who are deficient in phorbol 12-myristate 13-acetate (PMA)-induced NETosis, did not release S100A8/A9 upon PMA stimulation. Moreover, we purified S100A8/A9 from the cytoplasmic fraction of neutrophils and found that S100A8/A9 could induce neutrophil activation, including adhesion and CD11b upregulation, indicating that this DAMP might amplify neutrophil activation.

更新日期：2022-01-11

点击分享查看原文

点击收藏

公开下载

阅读更多本刊新发论文本刊介绍/投稿指南