Epidermal growth factor receptor signaling mediates regranulation of rat nasal goblet cells
Epidermal growth factor receptor signaling mediates regranulation of rat nasal goblet cells
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DOI：
10.1067/mai.2001.115140
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发表时间：
2001-06-01
影响因子：
14.2
通讯作者：
Nadel, JA
中科院分区：
文献类型：
--
作者：
Lee, HM;Malm, L;Nadel, JA
背景资料：粘液高分泌是下呼吸道炎症的常见反应，也是慢性鼻炎的标志。目的：探讨慢性鼻炎患者粘液再颗粒形成的机制（粘液产生），方法：由于中性粒细胞诱导表皮生长因子（EGFR）级联反应，我们通过鼻内吸入N-甲酰-甲硫氨酰-亮氨酰-苯丙氨酸（fMLP）诱导大鼠鼻呼吸道上皮中杯状细胞的脱颗粒。结果：在对照状态下，Alcian blue/periodic acid-Schiff染色和粘蛋白MUC 5AC染色均可见。鼻内吸入fMLP（10（-7）mol/L）4小时后，鼻中隔上皮细胞出现脱颗粒，48小时后，杯状细胞再颗粒形成完成。在对照状态下，上皮中不存在EGFR蛋白染色，但在fMLP诱导的脱粒后。EGFR蛋白表达。经选择性EGFR酪氨酸激酶抑制剂BIBX 1522预处理后，fMLP诱导的脱颗粒未受影响，但杯状细胞再颗粒形成被完全阻止。结论：这些数据表明EGFR级联在嗜酸性粒细胞依赖性杯状细胞粘蛋白产生中的作用，证明这一理论将需要在鼻分泌过多状态的临床研究中使用选择性EGFR抑制剂。
Background: Mucus hypersecretion is a common response to inflammation in the lower airways and is a hallmark of chronic rhinitis,Objective: The purpose of this study was to elucidate the mechanisms of regranulation (mucus production) of goblet cells in nasal epithelium,Methods: Because neutrophils induce an epidermal growth Factor (EGFR) cascade, we induced degranulation of goblet cells in rat nasal respiratory epithelium by means of intranasal inhalation of N-formyl-methionyl-leucyl-phenylalanine (fMLP). and we examined regranulation of the goblet cells and the role of EGFR inhibitors and neutrophils in the regranulation process.Results: In the control state Alcian blue/periodic acid-Schiff and mucin MUC5AC staining was present. Degranulation was induced in the nasal septal epithelium 4 hours after intranasal inhalation of fMLP (10(-7) mol/L): 48 hours later, goblet-cell regranulation was complete. In the control state EGFR protein staining was absent in the epithelium, but after fMLP-induced degranulation. EGFR protein was expressed. After pretreatment with BIBX1522, a selective EGFR tyrosine kinase inhibitor, fMLP-induced degranulation was unaffected, but goblet-cell regranulation was prevented completely,Conclusion: These data suggest a role for the EGFR cascade in neutrophil-dependent production of goblet-cell mucins, Proving this theory will require the use of selective EGFR inhibitors in clinical studies of nasal hypersecretory states.