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


CONCLUSIONS
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.
Lee
H M
HM
Cardiovascular Research Institute, University of California, San Francisco, CA 94143-0130, USA.
Malm
L
L
Dabbagh
K
K
Dao-Pick
T
T
Ueki
I F
IF
Kim
S
S
Shim
J J
JJ
Nadel
J A
JA
D000281:Administration, Intranasal; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020397:Goblet Cells / Q000502:physiology*; D008297:Male; D055271:Mucin 5AC; D009077:Mucins / Q000378:metabolism; D009093:Mucus / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000008:administration & dosage; D009297:Nasal Mucosa / Q000166:cytology* / Q000276:immunology; D018375:Neutrophil Activation / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction
D004791:Enzyme Inhibitors; C524680:Muc5ac protein, rat; D055271:Mucin 5AC; D009077:Mucins; D009240:N-Formylmethionine Leucyl-Phenylalanine; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases