Prevention of lung injury by Muc1 mucin in a mouse model of repetitive Pseudomonas aeruginosa  infection.
OBJECTIVE
To determine whether repetitive airway Pseudomonas aeruginosa (Pa) infection results in lung inflammation and injury and, if so, whether these responses are affected by Muc1 mucin. Muc1 wild type (WT) and knockout (KO) mice were compared for body weights, lung inflammatory responses, and airspace enlargement using a chronic lung infection model system.


METHODS
Mice were treated intranasally with Pa (10(7) CFU) on days 0, 4, 7 and 10. On day 14, body weights, inflammatory cell numbers in bronchoalveolar lavage fluid (BALF), and airspace enlargement were measured. Differences in inflammatory responses between groups were statistically analyzed by the Student's t test and ANOVA.


RESULTS
Muc1 WT mice exhibited mild degrees of both inflammation and airspace enlargement following repetitive airway Pa infection. However, Muc1 KO mice exhibited significantly decreased body weights, greater macrophage numbers in the BALF, and increased airspace enlargement compared with Muc1 WT mice.


CONCLUSIONS
This is the first report demonstrating that Muc1 deficiency can lead to lung injury during chronic Pa infection in mice. These results suggest that MUC1 may play a crucial role in the resolution of inflammation during chronic respiratory infections and that MUC1 dysfunction likely contributes to the pathogenesis of chronic inflammatory respiratory disease.
Center for Inflammation, Translational and Clinical Lung Research, Temple University School of Medicine, Philadelphia, PA 19140,, USA.
Tsuyoshi
T
Umehara
Kosuke
K
Kato
Yong Sung
YS
Park
Erik P
EP
Lillehoj
Hideyuki
H
Kawauchi
Kwang Chul
KC
Kim
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002452:Cell Count; D004195:Disease Models, Animal; D016209:Interleukin-8 / Q000378:metabolism; D055370:Lung Injury / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018396:Mucin-1 / Q000235:genetics / Q000378:metabolism*; D011552:Pseudomonas Infections / Q000378:metabolism*; D011550:Pseudomonas aeruginosa; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016209:Interleukin-8; D018396:Mucin-1; D014409:Tumor Necrosis Factor-alpha; C577056:muc1 protein, mouse