Muc-5/5ac Mucin Messenger RNA and Protein Expression Is a Marker of Goblet Cell Metaplasia in Murine Airways
- 1 March 2000
- journal article
- Published by American Thoracic Society in American Journal of Respiratory Cell and Molecular Biology
- Vol. 22 (3), 253-260
- https://doi.org/10.1165/ajrcmb.22.3.3768
Abstract
Airway inflammation, hyperreactivity, increased number of goblet cells, and mucus overproduction characterize asthma. Respiratory challenge with ovalbumin (OVA) of sensitized mice has been shown by several laboratories to cause pulmonary pathology similar to that observed in human allergic asthma. Recently, interleukin (IL)-13 has been shown to be a central mediator in this process. Because the airways of healthy mice have few, if any, mucus-producing cells, an increase in the number of these cells likely reflects induction of mucin-gene expression. The purpose of this study was to identify mucin genes induced as a result of airway goblet-cell metaplasia (GCM) in mice sensitized and challenged with OVA or in mice treated with IL-13 alone. BALB/c mice were sensitized by intraperitoneal injection (Days 0, 4, 7, 11, and 14) and intranasal instillation (Day 14) of 100 microg of OVA in saline, and then challenged by intranasal instillation (Days 25, 26, and 27) of the same. IL-13-treated mice received 5 microg of IL-13 by intranasal instillation on three consecutive days. Control mice were given saline alone. All mice were studied 24 h after the last challenge. Histologic analysis of the lungs revealed both a striking peribronchial and perivascular lymphocytic and eosinophilic inflammation and airway GCM in OVA-treated mice, and also airway GCM without inflammation in IL-13-treated mice. Northern blot analysis of lung RNA demonstrated (1) expression of Muc-5/5ac messenger RNA (mRNA) in OVA-treated and IL-13-treated mice, but not in control mice; (2) expression of Muc-1 mRNA at comparable levels in all mice regardless of treatment; and (3) no expression of Muc-2 or Muc-3 mRNA in control or treated mice. Western blot analysis demonstrated the expression of Muc-5/5ac protein (both apomucin and glycosylated mucin) in lung lysates of OVA-treated (but not control) mice, and also the expression of Muc-5/5ac mucins in the bronchoalveolar lavage fluid of OVA-treated and IL-13-treated mice. These findings demonstrate that airway GCM is associated with the induction of pulmonary expression of Muc-5/5ac mRNA and mucin in murine models of allergic asthma.Keywords
This publication has 45 references indexed in Scilit:
- PDB2MultiGIF: A Web Tool to Create Animated Images of MoleculesJournal of Molecular Modeling, 1998
- Interleukin-5 Expression in the Lung Epithelium of Transgenic Mice Leads to Pulmonary Changes Pathognomonic of AsthmaThe Journal of Experimental Medicine, 1997
- Airway structure and inflammatory cells in fatal attacks of asthmaEuropean Respiratory Journal, 1996
- Epithelial Mucin GenesAnnual Review of Physiology, 1995
- Pulmonary macrophagesEuropean Respiratory Journal, 1994
- Expression of MUC1, MUC2, MUC3 and MUC4 mucin mrnas in human pancreatic and intestinal tumor cell linesInternational Journal of Cancer, 1994
- Expression of human mucin genes in respiratory, digestive, and reproductive tracts ascertained by in situ hybridization.Journal of Histochemistry & Cytochemistry, 1993
- Aerosolized antigen exposure without adjuvant causes increased IgE production and increased airway responsiveness in the mouseJournal of Allergy and Clinical Immunology, 1992
- The relationship between airway inflammation and bronchial hyperresponsivenessClinical and Experimental Allergy, 1989
- Expression of the alpha-1-antitrypsin gene in mononuclear phagocytes of normal and alpha-1-antitrypsin-deficient individuals.JCI Insight, 1986