Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.
Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill.
J Allergy Clin Immunol. 2022 May;149(5):1666-1674. doi: 10.1016/j.jaci.2021.11.023. Epub 2021 Dec 22.
Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) is well characterized by type 2 (T2) inflammation characterized by eosinophilia in Western countries. However, the presence and roles of neutrophils in T2 CRSwNP are poorly understood.
We sought to clarify accumulation and inflammatory roles of neutrophils in CRSwNP in a Western population.
Sinonasal tissues and nasal lavage fluids were obtained from control patients and patients with CRS, and neutrophil markers were determined by ELISA. The presence of neutrophils in tissue was determined by flow cytometry. The gene expression profiles in neutrophils were determined by RNA sequencing.
A neutrophil marker elastase was selectively elevated in nasal polyp (NP) tissue, whereas eosinophilic cationic protein (an eosinophil marker) was elevated in both uncinate and NP tissues of CRSwNP patients. Nasal lavage fluid myeloperoxidase (another neutrophil marker) was also significantly elevated in CRSwNP compared to control patients. Neutrophil markers were more greatly elevated in CRSwNP patients with recurrent disease. Flow cytometric analysis confirmed that neutrophil numbers were significantly elevated in NPs compared to control tissues. RNA sequencing analysis found that 344 genes were >3-fold and significantly elevated in NP neutrophils compared to peripheral blood neutrophils. Gene Ontology analysis suggested that the elevated genes in NP neutrophils were significantly associated with activation. Results suggest that neutrophils are accumulated in T2 NP tissues and that accumulated neutrophils are highly activated and contribute to inflammation in NPs.
Neutrophils may play a heretofore unrecognized meaningful role in the pathogenesis of CRSwNP in Western countries and may be a potentially important therapeutic target in T2 CRSwNP.
在西方国家，慢性鼻-鼻窦炎伴鼻息肉（CRSwNP）的特征是 2 型（T2）炎症，表现为嗜酸性粒细胞增多。然而，在 T2 CRSwNP 中，中性粒细胞的存在和作用仍知之甚少。
我们旨在阐明西方人群中 CRSwNP 中中性粒细胞的积累和炎症作用。
从对照患者和 CRS 患者中获取鼻-鼻窦组织和鼻洗液，并通过 ELISA 测定中性粒细胞标志物。通过流式细胞术测定组织中中性粒细胞的存在。通过 RNA 测序测定中性粒细胞的基因表达谱。
中性粒细胞标志物弹性蛋白酶选择性地在鼻息肉（NP）组织中升高，而嗜酸性阳离子蛋白（一种嗜酸性粒细胞标志物）在 CRSwNP 患者的钩突和 NP 组织中均升高。与对照患者相比，CRSwNP 患者的鼻洗液髓过氧化物酶（另一种中性粒细胞标志物）也显著升高。在有复发性疾病的 CRSwNP 患者中，中性粒细胞标志物的升高更为显著。流式细胞术分析证实，与对照组织相比，NP 中的中性粒细胞数量显著升高。RNA 测序分析发现，与外周血中性粒细胞相比，NP 中性粒细胞中 344 个基因的表达上调了 3 倍以上，且显著上调。GO 分析表明，NP 中性粒细胞中上调的基因与激活显著相关。结果表明，中性粒细胞在 T2 NP 组织中积累，并且积累的中性粒细胞高度激活并有助于 NP 中的炎症。
中性粒细胞可能在西方国家的 CRSwNP 发病机制中发挥了迄今为止尚未被认识的重要作用，并且可能是 T2 CRSwNP 中一个潜在的重要治疗靶点。
