Division of Otorhinolaryngology Head and Neck Surgery, Department of Sensory and Locomotor Medicine, University of Fukui, Fukui, Japan.
Department of Molecular Biology and Chemistry, University of Fukui, Fukui, Japan.
Allergy. 2019 Jul;74(7):1307-1316. doi: 10.1111/all.13677. Epub 2018 Dec 17.
Most patients with nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (NERD) suffer from recurrence of nasal polyps. However, little is known about the specific cellular and molecular mechanisms contributing to the pathogenesis of nasal polyp development in patients with NERD in particular, especially at baseline when cyclooxygenase 1 inhibitors are not present. The objectives of this study were to identify proteins involved in the pathogenesis of nasal polyps in patients with NERD.
We collected nasal polyp tissue from patients with NERD and from patients with aspirin-tolerant chronic rhinosinusitis with nasal polyps (CRSwNP). Protein profiles were analyzed by 2-dimensional electrophoresis and identified several proteins, including L-plastin, as highly expressed. We examined L-plastin and tissue factor (TF) expression by immunohistochemical and immunofluorescence analyses. To examine the role of L-plastin in eosinophils, we knocked down L-plastin expression in Eol-1 cells by using siRNA transfection.
L-plastin protein levels in nasal polyp tissue were increased in patients with NERD relative to those in patients with aspirin tolerant CRSwNP. Immunofluorescence analysis revealed that L-plastin was dominantly expressed in eosinophils and L-plastin and TF were co-expressed in eosinophils in NERD nasal polyp tissue. Knockdown of L-plastin in Eol-1 cells disrupted the cell surface distribution of TF by stimulation with granulocyte macrophage colony-stimulating factor.
Increased expression of L-plastin by eosinophils may contribute to abnormal fibrin deposition through TF translocation to the eosinophil cell surface in NERD nasal polyp tissue, which in turn may contribute to the pathogenesis of NERD.
大多数非甾体抗炎药加重的呼吸道疾病（NERD）患者会出现鼻息肉复发。然而，对于 NERD 患者，尤其是在环氧化酶 1 抑制剂不存在时，鼻息肉发展的发病机制中具体的细胞和分子机制知之甚少。本研究的目的是鉴定 NERD 患者鼻息肉发病机制中涉及的蛋白。
我们收集了 NERD 患者和阿司匹林耐受的慢性鼻-鼻窦炎伴鼻息肉（CRSwNP）患者的鼻息肉组织。通过二维电泳分析蛋白质谱，并鉴定出包括 L-肌动蛋白在内的几种高表达蛋白。我们通过免疫组化和免疫荧光分析检测 L-肌动蛋白和组织因子（TF）的表达。为了研究 L-肌动蛋白在嗜酸性粒细胞中的作用，我们通过 siRNA 转染敲低了 Eol-1 细胞中的 L-肌动蛋白表达。
与阿司匹林耐受的 CRSwNP 患者相比，NERD 患者鼻息肉组织中的 L-肌动蛋白蛋白水平增加。免疫荧光分析显示，L-肌动蛋白在嗜酸性粒细胞中表达丰富，L-肌动蛋白和 TF 在 NERD 鼻息肉组织的嗜酸性粒细胞中共同表达。用粒细胞-巨噬细胞集落刺激因子刺激后，Eol-1 细胞中 L-肌动蛋白的敲低破坏了 TF 的细胞表面分布。
嗜酸性粒细胞中 L-肌动蛋白的表达增加可能通过 TF 向嗜酸性粒细胞表面的易位导致 NERD 鼻息肉组织中异常纤维蛋白沉积，从而有助于 NERD 的发病机制。
