fMLP causes degranulation followed by regranulation in rat nasal glands.
OBJECTIVE
To determine the mechanism of mucus production by nasal glands.


METHODS
Because neutrophilic inflammation is associated with mucus hypersecretion in disease states, here we examine the role of neutrophil recruitment in mucous cell degranulation and regranulation in rat nasal glands.


METHODS
N-formyl-methionyl-leucyl-phenylalanine (fMLP) was aerosolized intranasally in rats (n = 5), and its effects on degranulation and regranulation of submucosal glands were evaluated by Alcian blue/periodic acid-Schiff (AB/PAS) staining and by immunolocalization of neutrophils and epidermal growth factor receptor (EGF-R).


RESULTS
In control subjects, glands were filled with mucin. After fMLP inhalation, degranulation, 31.7 +/- 0.8% (P <.01), was maximal at 2 to 4 hours. By 24 to 48 hours after fMLP inhalation, degranulation had decreased to 10.3 +/- 0.6% (P <.05), indicating that regranulation of mucous glycoconjugates was occurring. After fMLP inhalation, neutrophils around submucosal glands increased within 0.5 hours from 1.4 +/- 0.1 to 9.5 +/- 0.3 per 0.0032 mm2 (P <.05). In control subjects, EGF-R protein was expressed near acinar ducts, 16.4 +/- 0.7% of gland area, and increased to 30.9 +/- 0.9% (P <.05) 24 to 48 hours after fMLP inhalation. Nasal pretreatment with a selective EGF-R tyrosine kinase inhibitor (BIBX1522, 15 mg/kg bid) prevented regranulation at 24 hours after fMLP inhalation (degranulation 27.8 +/- 0.3%, P <.05, compared to 24 hours after fMLP alone), indicating that inhibition of EGF-R activation had prevented regranulation after fMLP inhalation.


CONCLUSIONS
Degranulation of rat nasal glands by fMLP is followed by regranulation; regranulation depends on a neutrophil-associated EGF-R cascade.
Kim
Seon-Tae
ST
Cardiovascular Research Institute and Department of Medicine, University of California, San Francisco 94143-0130, USA.
Nakanaga
Takashi
T
Ueki
Iris
I
Nadel
Jay A
JA
D000818:Animals; D015550:Cell Degranulation / Q000187:drug effects*; D066246:ErbB Receptors / Q000378:metabolism; D006097:Granulation Tissue / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000009:adverse effects*; D009297:Nasal Mucosa / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D009504:Neutrophils / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism
D066246:ErbB Receptors; D009240:N-Formylmethionine Leucyl-Phenylalanine; D018719:Erb-b2 Receptor Tyrosine Kinases; C064740:epidermal growth factor receptor-neu receptor