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 mucin gene expression (MUC2 and MUC5ac) are associated with histological signs of mucus hypersecretion, rats were exposed to acrolein (3.0 parts/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 histochemical 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 the surface of the airways and in submucosal gland epithelium. By comparison, increases in lung MUC5ac mRNA and mucin glycoproteins were delayed and were elevated after exposures on days 5 and 9, respectively. Increased MUC5ac immunostaining was detected within the lumen and airway epithelium of the lung on day 12. In contrast, MUC2 mRNA levels were not significantly changed in the trachea or lung. These findings indicate that acrolein-induced mucus hypersecretion is due, in part, to increases in MUC5ac rather than to MUC2 gene expression. These findings suggest that aldehyde-induced increases in MUC5ac may play a role in chronic mucus hypersecretion, a pathognomonic feature of chronic obstructive pulmonary disease.
Borchers
M T
MT
Department of Environmental Health, University of Cincinnati 45267, USA.
Wert
S E
SE
Leikauf
G D
GD
D000171:Acrolein / Q000494:pharmacology*; D000818:Animals; D007150:Immunohistochemistry; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009077:Mucins / Q000235:genetics / Q000378:metabolism*; D009994:Osmolar Concentration; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014132:Trachea / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
D009077:Mucins; D012333:RNA, Messenger; D000171:Acrolein