Burgel P R, Escudier E, Coste A, Dao-Pick T, Ueki I F, Takeyama K, Shim J J, Murr A H, Nadel J A
Cardiovascular Research Institute and Departments of Medicine and Physiology, University of California San Francisco, San Francisco, CA 94143-0130, USA.
J Allergy Clin Immunol. 2000 Oct;106(4):705-12. doi: 10.1067/mai.2000.109823.
Because the epidermal growth factor receptor (EGFR) system regulates mucin production in airway epithelium, we hypothesized a role for this system in mucus hypersecretion that occurs in nasal polyposis.
We examined the relationship between goblet cell hyperplasia, EGFR expression, and inflammatory mediators produced by eosinophils and neutrophils in nasal polyp tissues.
Nasal polyp tissue samples from 8 patients and nasal turbinate biopsy specimens from 6 normal control subjects were examined for alcian blue/PAS staining, mucin MUC5AC (MUC5AC), and EGFR immunoreactivity and EGFR gene expression (in situ hybridization). We also examined the role of eosinophils and neutrophils in goblet cell hyperplasia.
In control nasal mucosa alcian blue/periodic acid-Schiff- and MUC5AC-stained areas were 18.40% +/- 1.31% and 21.89% +/- 1.43%, respectively. In polyps the alcian blue/periodic acid-Schiff- and MUC5AC-stained areas were 51.30% +/- 5.85% and 52.07% +/- 6.58%, which was significantly larger than that found in control subjects (each comparison, P <.01). Four of 6 control specimens expressed EGFR messenger RNA and protein weakly in the epithelium. In polyps 4 of 8 specimens expressed EGFR gene and EGFR protein strongly; the EGFR-stained area was greater in hyperplastic than in pseudostratified epithelium. TNF-alpha immunoreactivity, expressed in eosinophils, was increased in EGFR-positive polyps compared with EGFR-negative polyps, suggesting a role for TNF-alpha in EGFR expression. Neutrophils were increased in the epithelium of EGFR-positive compared with EGFR-negative polyps, suggesting a role for these cells in mucin expression and in goblet cell degranulation.
These data suggest a role for EGFR cascade in the regulation of goblet cell mucins in nasal polyps. Proof of concept will require clinical studies using selective EGFR inhibitors.
由于表皮生长因子受体（EGFR）系统调节气道上皮中的黏蛋白产生，我们推测该系统在鼻息肉中出现的黏液分泌过多中发挥作用。
我们研究了鼻息肉组织中杯状细胞增生、EGFR表达以及嗜酸性粒细胞和中性粒细胞产生的炎症介质之间的关系。
对8例患者的鼻息肉组织样本和6例正常对照受试者的鼻甲活检标本进行阿尔辛蓝/过碘酸希夫染色、黏蛋白MUC5AC（MUC5AC）、EGFR免疫反应性和EGFR基因表达（原位杂交）检测。我们还研究了嗜酸性粒细胞和中性粒细胞在杯状细胞增生中的作用。
在对照鼻黏膜中，阿尔辛蓝/过碘酸希夫染色和MUC5AC染色区域分别为18.40%±1.31%和21.89%±1.43%。在息肉中，阿尔辛蓝/过碘酸希夫染色和MUC5AC染色区域分别为51.30%±5.85%和52.07%±6.58%，显著大于对照受试者（每次比较，P<.01）。6例对照标本中有4例在上皮中弱表达EGFR信使核糖核酸和蛋白。在息肉中，8例标本中有4例强烈表达EGFR基因和EGFR蛋白；增生上皮中EGFR染色区域大于假复层上皮。与EGFR阴性息肉相比，EGFR阳性息肉中嗜酸性粒细胞表达的肿瘤坏死因子-α免疫反应性增加，提示肿瘤坏死因子-α在EGFR表达中发挥作用。与EGFR阴性息肉相比，EGFR阳性息肉上皮中的中性粒细胞增加，提示这些细胞在黏蛋白表达和杯状细胞脱颗粒中发挥作用。
这些数据提示EGFR级联在鼻息肉中杯状细胞黏蛋白的调节中发挥作用。概念验证将需要使用选择性EGFR抑制剂的临床研究。
