Upper Airways Research Laboratory, Faculty of Medicine, Ghent University, Ghent, Belgium.
Laboratory of Virology, Faculty of Veterinary Medicine, Ghent University, Ghent University, Ghent, Belgium.
J Allergy Clin Immunol. 2021 Jan;147(1):179-188.e2. doi: 10.1016/j.jaci.2020.08.036. Epub 2020 Sep 16.
Chronic rhinosinusitis with nasal polyps (CRSwNP) is generally associated with severe type 2 immune reactions in the white population. However, recent findings suggest an additional role for neutrophils in severe type 2 inflammation.
This study aimed to characterize the neutrophilic inflammation in CRSwNP and its relation to eosinophilic inflammation in severe type 2 immune reactions.
The presence and activation of neutrophils and eosinophils was analyzed in CRS without NP and CRSwNP by measuring cell and activation markers via immunohistochemistry, immunofluorescence, Luminex assay, ELISA, UniCAP, fluorescence-activated cell sorting, and PCR. Differential neutrophil migration was assessed via Boyden-chamber assay and neutrophil survival was analyzed via flow cytometry.
Both CRS without NP and CRSwNP displayed variable degrees of eosinophilic and neutrophilic inflammation, with a profound neutrophilic infiltration and activation in type 2 CRSwNP, associated with eosinophil extracellular traps cell death and Charcot-Leyden crystals, but independent of IL-17. Neutrophil extracellular traps cell death in CRSwNP was associated with bacterial colonization, however, neutrophils were less prone to undergo neutrophil extracellular traps cell death in the tissue of patients with severe type 2 CRSwNP. Neutrophils did not show increased migration nor survival in the CRSwNP environment in vitro.
This study demonstrated a severe neutrophilic inflammation associated with severe eosinophilic type 2 inflammatory CRSwNP, the role of which needs further study.
慢性鼻-鼻窦炎伴鼻息肉(CRSwNP)通常与白种人群中的严重 2 型免疫反应有关。然而,最近的研究结果表明中性粒细胞在严重 2 型炎症中发挥了额外的作用。
本研究旨在描述 CRSwNP 中的中性粒细胞炎症及其与严重 2 型免疫反应中的嗜酸性粒细胞炎症的关系。
通过免疫组织化学、免疫荧光、Luminex assay、ELISA、UniCAP、荧光激活细胞分选和 PCR 测量细胞和激活标志物,分析无 NP 的 CRS 和 CRSwNP 中中性粒细胞和嗜酸性粒细胞的存在和激活。通过 Boyden 室测定评估差异中性粒细胞迁移,通过流式细胞术分析中性粒细胞存活。
无 NP 的 CRS 和 CRSwNP 均显示出不同程度的嗜酸性粒细胞和中性粒细胞炎症,2 型 CRSwNP 中存在明显的中性粒细胞浸润和激活,与嗜酸性粒细胞细胞外陷阱细胞死亡和夏科-莱登晶体有关,但与 IL-17 无关。然而,在严重 2 型 CRSwNP 患者的组织中,中性粒细胞细胞外陷阱细胞死亡与细菌定植有关,但中性粒细胞不太容易发生中性粒细胞细胞外陷阱细胞死亡。在体外,中性粒细胞在 CRSwNP 环境中没有增加迁移或存活。
本研究表明与严重嗜酸性粒细胞 2 型炎症 CRSwNP 相关的严重中性粒细胞炎症,其作用需要进一步研究。