ACROLEIN-INDUCED MUC5AC EXPRESSION IN RAT AIRWAYS

Acrolein, a low-molecular-weight aldehyde found in photochemical smog and tobacco smoke, can induce mucus hypersecretion, inflammation, and airway hyperreactivity. To determine whether changes in steady-state m ucin gene expression (MUC2 and MUC5ac) are associated with histologica l signs of mucus hypersecretion, rats were exposed to acrolein (3.0 pa rts/million, 6 h/day, 5 days/wk, 2 wk), and the trachea with the main stem bronchi was separated from the intrapulmonary airways (lung). The temporal expression of MUC2 and MUC5ac mRNA was determined by RT-PCR, and acidic mucin glycoproteins were detected by Alcian blue histochem ical analysis. MUC5ac protein content in the airways was determined by immunohistochemical analysis. Tracheal MUC5ac mRNA increased within 2 days and was accompanied by an increase in MUC5ac immunostaining on t he surface of the airways and in submucosal gland epithelium. By compa rison, increases in lung MUC5ac mRNA and mucin glycoproteins were dela yed and were elevated after exposures on days 5 and 9, respectively. I ncreased MUC5ac immunostaining was detected within the lumen and airwa y epithelium of the lung on day 12. In contrast, MUC2 mRNA levels were not significantly changed in the trachea or lung. These findings indi cate that acrolein-induced mucus hypersecretion is due, in part, to in creases in MUC5ac rather than to MUC2 gene expression. These findings suggest that aldehyde-induced increases in MUC5ac may play a role in c hronic mucus hypersecretion, a pathognomonic feature of chronic obstru ctive pulmonary disease.