fMLP causes degranulation followed by regranulation in rat nasal glands

Authors

  • Seon-Tae Kim MD, PhD,

    1. Cardiovascular Research Institute and Departments of Medicine and Physiology, University of California, San Francisco, San Francisco, California, U.S.A.
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  • Takashi Nakanaga MD,

    1. Cardiovascular Research Institute and Departments of Medicine and Physiology, University of California, San Francisco, San Francisco, California, U.S.A.
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  • Iris Ueki BA,

    1. Cardiovascular Research Institute and Departments of Medicine and Physiology, University of California, San Francisco, San Francisco, California, U.S.A.
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  • Jay A. Nadel MD

    Corresponding author
    1. Cardiovascular Research Institute and Departments of Medicine and Physiology, University of California, San Francisco, San Francisco, California, U.S.A.
    • Jay A. Nadel, MD, Cardiovascular Research Institute, Box 0130, University of California, San Francisco, San Francisco, CA 94143-0130, U.S.A.
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Abstract

Objective: To determine the mechanism of mucus production by nasal glands. Study Design: 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.

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