Monocyte inflammation augments acrolein-induced Muc5ac expression in mouse lung.
Acrolein, an unsaturated aldehyde found in smog and tobacco smoke, can induce airway hyperreactivity, inflammation, and mucus hypersecretion. To determine whether changes in steady-state mucin gene expression (Muc2 and Muc5ac) are associated with inflammatory cell accumulation and neutrophil elastase activity, FVB/N mice were exposed to acrolein (3.0 parts/million; 6 h/day, 5 days/wk for 3 wk). The levels of Muc2 and Muc5ac mRNA were determined by RT-PCR, and the presence of Muc5ac protein was detected by immunohistochemistry. Total and differential cell counts were determined from bronchoalveolar lavage (BAL) fluid, and neutrophil elastase activity was measured in the BAL fluid supernatant. Lung Muc5ac mRNA was increased on days 12 and 19, and Muc5ac protein was detected in mucous granules and on the surface of the epithelium on day 19. Lung Muc2 mRNA was not detected at measurable levels in either control or exposed mice. Acrolein exposure caused a significant and persistent increase in macrophages and a rapid but transient increase in neutrophils in BAL fluid. Recoverable neutrophil elastase activity was not significantly altered at any time after acrolein exposure. To further examine the role of macrophage accumulation in mucin gene expression, additional strains of mice (including a strain genetically deficient in macrophage metalloelastase) were exposed to acrolein for 3 wk, and Muc5ac mRNA levels and macrophage accumulation were measured. The magnitude of macrophage accumulation coincided with increased Muc5ac mRNA levels, indicating that excessive macrophage accumulation augments acrolein-induced Muc5ac synthesis and secretion after repeated exposure. These findings support a role for chronic monocytic inflammation in the pathogenesis of mucus hypersecretion observed in chronic bronchitis.
Borchers
M T
MT
Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati 45267, Ohio, USA.
Wesselkamper
S
S
Wert
S E
SE
Shapiro
S D
SD
Leikauf
G D
GD
D000171:Acrolein / Q000494:pharmacology*; D000818:Animals; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D053508:Matrix Metalloproteinase 12; D008666:Metalloendopeptidases / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout / Q000235:genetics; D009000:Monocytes / Q000473:pathology / Q000502:physiology*; D055271:Mucin 5AC; D055262:Mucin-2; D009077:Mucins / Q000235:genetics / Q000378:metabolism*; D011014:Pneumonia / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D013045:Species Specificity
C524626:Muc2 protein, mouse; C524679:Muc5ac protein, mouse; D055271:Mucin 5AC; D055262:Mucin-2; D009077:Mucins; D012333:RNA, Messenger; D000171:Acrolein; D008666:Metalloendopeptidases; D053508:Matrix Metalloproteinase 12