Muc-5/5ac mucin messenger RNA and protein expression is a marker of gobletcell metaplasia in murine airways

Airway inflammation, hyperreactivity, increased number of goblet cells, and mucus overproduction characterize asthma. Respiratory challenge with ovalb umin (OVA) of sensitized mice has been shown by several laboratories to cau se pulmonary pathology similar to that observed in human allergic asthma. R ecently, interleukin (IL)-13 has been shown to be a central mediator in thi s process. Because the airways of healthy mice have few, if any, mucus-prod ucing cells, an increase in the number of these cells likely reflects induc tion of mucin-gene expression. The purpose of this study was to identify mu cin genes induced as a result of airway goblet-cell metaplasia (GCM) in mic e sensitized and challenged with OVA or in mice treated with IL-13 alone. B ALB/c mice were sensitized by intraperitoneal injection (Days 0, 4, 7, 11, and 14) and intranasal instillation (Day 14) of 100 mu g of OVA in saline, and then challenged by intranasal instillation (Days 25, 26, and 27) of the same. IL-13-treated mice received 5 mu g of IL-13 by intranasal instillati on on three consecutive days. Control mice were given saline alone. All mic e were studied 24 h after the last challenge. Histologic analysis of the lu ngs revealed both a striking peribronchial and perivascular lymphocytic and eosinophilic inflammation and airway GCM in OVA-treated mice, and also air way GCM without inflammation in IL-13-treated mice. Northern blot analysis of lung RNA demonstrated (1) expression of Muc-5/5ac messenger RNA (mRNA) i n OVA-treated and IL-13-treated mice, but not in control mice; (2) expressi on 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. We stern blot analysis demonstrated the expression of Muc-5/5ac protein (both apomucin and glycosylated mucin) in lung lysates of OVA-treated (but not co ntrol) mice, and also the expression of Muc-5/5ac mucins in the bronchoalve olar lavage fluid of OVA-treated and IL-13-treated mice. These findings dem onstrate that airway GCM is associated with the induction of pulmonary expr ession of Muc-5/5ac mRNA and mucin in murine models of allergic asthma.