Department of Otorhinolaryngology, Jikei University School of Medicine, Tokyo, Japan.
Int Arch Allergy Immunol. 2013;161 Suppl 2:138-46. doi: 10.1159/000350386. Epub 2013 May 29.
A recent study suggested that protease-activated receptors (PARs) are involved in allergic respiratory diseases, such as asthma. Chronic rhinosinusitis (CRS) is one of the most common chronic airway diseases, but little is understood about its pathogenesis. The purpose of this study was to compare the expression and distribution of PARs in biopsy specimens obtained from CRS and control patients.
Biopsy specimens were obtained from 7 pituitary tumor patients as controls, 8 CRS patients with aspirin-tolerant asthma (ATA), 7 CRS patients with aspirin-induced asthma (AIA), and 7 CRS patients without asthma (CRS). Sections were stained for PAR-1, PAR-2, PAR-3 and PAR-4 using specific polyclonal antibodies. Staining was scored semiquantitatively for both intensity and distribution. To confirm the presence of PARs on inflammatory cells, double staining with eosinophil cationic protein (EG2) and elastase was also performed.
Both the epithelium and the infiltrating inflammatory cells in the CRS with asthma groups showed significant upregulation of the expression of PAR-2 and PAR-3 compared with the CRS without asthma group and the control group. In the patients with CRS complicated by asthma, eosinophils were increased among PAR-2- and PAR-3-positive cells. In the patients with CRS not complicated by asthma, neutrophils were increased among PAR-2-positive cells.
Differences in the expression of PAR-2 and PAR-3 on epithelial cells, eosinophils and neutrophils may be involved in the pathogenesis of CRS. CRS may be able to be treated by targeting PAR-2 and PAR-3.
最近的一项研究表明,蛋白酶激活受体(PARs)参与了过敏性呼吸道疾病,如哮喘。慢性鼻-鼻窦炎(CRS)是最常见的慢性气道疾病之一,但对其发病机制知之甚少。本研究旨在比较从 CRS 和对照患者获得的活检标本中 PARs 的表达和分布。
从 7 例垂体瘤患者作为对照、8 例阿司匹林耐受性哮喘(ATA)CRS 患者、7 例阿司匹林诱导性哮喘(AIA)CRS 患者和 7 例无哮喘的 CRS 患者(CRS)中获得活检标本。使用特异性多克隆抗体对 PAR-1、PAR-2、PAR-3 和 PAR-4 进行染色。对染色强度和分布进行半定量评分。为了确认 PARs 是否存在于炎症细胞上,还进行了嗜酸性粒细胞阳离子蛋白(EG2)和弹性蛋白酶的双染色。
与无哮喘的 CRS 组和对照组相比,哮喘合并 CRS 组的上皮细胞和浸润性炎症细胞中 PAR-2 和 PAR-3 的表达均显著上调。在哮喘合并 CRS 的患者中,PAR-2 和 PAR-3 阳性细胞中嗜酸性粒细胞增加。在不伴哮喘的 CRS 患者中,PAR-2 阳性细胞中中性粒细胞增加。
上皮细胞、嗜酸性粒细胞和中性粒细胞中 PAR-2 和 PAR-3 表达的差异可能参与了 CRS 的发病机制。靶向 PAR-2 和 PAR-3 可能有助于治疗 CRS。