Epidermal growth factor receptor signaling mediates regranulation of rat nasal goblet cells

• Published in: Journal of allergy and clinical immunology 2001-06, Vol.107 (6), p.1046-1050
• Main Authors: Lee, Heung-Man, Malm, Lars, Dabbagh, Karim, Dao-Pick, Trang, Ueki, Iris F., Kim, Suil, Shim, Jae Jeong, Nadel, Jay A.
• Format: Article
• Language: English
• Subjects: Administration, Intranasal; Animals; Biological and medical sciences; Enzyme Inhibitors - pharmacology; epidermal growth factor receptor cascade; epidermal growth factor receptor tyrosine kinase activation; epidermal growth factor receptors; Goblet Cells - physiology; Male; Medical sciences; Mucin 5AC; mucin expression; Mucins - metabolism; Mucus - secretion; N-formyl-Met-Leu-Phe; N-Formylmethionine Leucyl-Phenylalanine - administration & dosage; nasal hypersecretion; Nasal Mucosa - cytology; Nasal Mucosa - immunology; Neutrophil Activation - immunology; Neutrophils - immunology; Non tumoral diseases; Otorhinolaryngology. Stomatology; Phosphorylation; Protein-Tyrosine Kinases - antagonists & inhibitors; Protein-Tyrosine Kinases - metabolism; Rats; Receptor, Epidermal Growth Factor - antagonists & inhibitors; Receptor, Epidermal Growth Factor - metabolism; Secretory cell growth; Signal Transduction; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1067/mai.2001.115140

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. (J Allergy Clin Immunol 2001;107:1046-50.)