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

Abstract

Mucus hypersecretion is a common response to inflammation in the lower airways and is a hallmark of chronic rhinitis. The purpose of this study was to elucidate the mechanisms of regranulation (mucus production) of goblet cells in nasal epithelium. 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. 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. 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.