Department of Otolaryngology-Head and Neck Surgery, Northwestern University Feinberg School of Medicine, Chicago, Ill 60607, USA.
J Allergy Clin Immunol. 2010 Mar;125(3):667-75. doi: 10.1016/j.jaci.2009.11.045.
Decreased epithelial expression of mRNA for S100A7 (psoriasin) and S100A8/A9 (calprotectin) has been reported in patients with chronic rhinosinusitis (CRS).
We sought to assess whether the expression of S100 proteins is also altered in the sinonasal cavity of patients with CRS.
We determined levels of S100 proteins in nasal lavage fluid and sinonasal tissue extracts from patients with CRS using ELISA and immunohistochemical analysis of nasal polyp tissue from patients with CRS with nasal polyps and uncinate tissue from healthy control subjects, patients with CRSsNP, and patients with CRSwNP.
Expression levels of S100 proteins were decreased compared with those seen in control subjects in nasal lavage fluid from both CRS groups (P < .05). Similarly, tissue expression of these proteins assessed by means of immunohistochemistry demonstrated clear reductions, primarily in the epithelial lining. Interestingly, levels of calprotectin were increased in nasal polyp tissue despite lower levels in lavage fluid. Levels of calprotectin in nasal tissues were correlated with levels of neutrophils, as assessed by means of quantification of neutrophil elastase.
Several S100 proteins are in the epidermal differentiation complex of genes and have been demonstrated to play a role in maintenance of barrier function and formation of an antimicrobial shield. We demonstrate significantly decreased levels of expression of S100 proteins in the epithelium of patients with CRS, which might lead to diminished innate immune responses and barrier function. Increased levels of calprotectin in nasal polyp tissue might reflect neutrophil recruitment and a compensatory mechanism. Future studies will be important to determine whether reduced levels of S100 proteins lead to decreased antimicrobial responses in the upper airways and sinuses and whether this reduction plays a causative role in CRS pathogenesis and susceptibility to infectious disease.
据报道,慢性鼻-鼻窦炎(CRS)患者的 S100A7(银屑病相关蛋白)和 S100A8/A9(钙卫蛋白)mRNA 的上皮细胞表达减少。
我们旨在评估 S100 蛋白的表达是否也在 CRS 患者的鼻-鼻窦腔内发生改变。
我们使用 ELISA 法和免疫组织化学分析,测定了 CRS 患者鼻腔灌洗液和鼻组织提取物中 S100 蛋白的水平,分析了伴有鼻息肉的 CRS 患者的鼻息肉组织和健康对照者、伴有 CRSsNP 的患者以及伴有 CRSwNP 的患者的鼻甲组织中的 S100 蛋白。
与对照组相比,两组 CRS 患者的鼻腔灌洗液中 S100 蛋白的表达水平均降低(P<0.05)。同样,通过免疫组织化学评估的这些蛋白的组织表达也显示出明显减少,主要在上皮衬里中。有趣的是,尽管鼻腔灌洗液中的 calprotectin 水平较低,但在鼻息肉组织中其水平却升高。鼻组织中 calprotectin 的水平与中性粒细胞弹性蛋白酶定量评估的中性粒细胞水平相关。
几种 S100 蛋白属于表皮分化复合物基因,已被证明在维持屏障功能和形成抗菌屏障方面发挥作用。我们发现 CRS 患者的上皮细胞中 S100 蛋白的表达水平显著降低,这可能导致固有免疫反应和屏障功能减弱。鼻息肉组织中 calprotectin 水平升高可能反映了中性粒细胞的募集和代偿机制。未来的研究将很重要,以确定 S100 蛋白水平降低是否导致上呼吸道和鼻窦的抗菌反应减弱,以及这种减少是否在 CRS 发病机制和对感染性疾病的易感性中起因果作用。