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Combined exposure to cigarette smoke and nontypeable Haemophilus influenzae drives development of a COPD phenotype in mice.

Ganesan S, Comstock AT, Kinker B, Mancuso P, Beck JM, Sajjan US - Respir. Res. (2014)

Bottom Line: CS/HK-NTHi-exposed mice also expressed increased levels of mucin genes and cytokines compared to mice in other groups.CS/HK-NTHi-exposed mice infected with RV demonstrated increased viral persistence, sustained neutrophilia, and further increments in mucin gene and chemokine expression compared to other groups.These findings indicate that in addition to CS, bacteria may also contribute to development of COPD, particularly changes in airways.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan, 1150 W, Medical Center Dr,, Ann Arbor, MI 48109-5688, USA. usajjan@umich.edu.

ABSTRACT

Background: Cigarette smoke (CS) is the major etiologic factor of chronic obstructive pulmonary disease (COPD). CS-exposed mice develop emphysema and mild pulmonary inflammation but no airway obstruction, which is also a prominent feature of COPD. Therefore, CS may interact with other factors, particularly respiratory infections, in the pathogenesis of airway remodeling in COPD.

Methods: C57BL/6 mice were exposed to CS for 2 h a day, 5 days a week for 8 weeks. Mice were also exposed to heat-killed non-typeable H. influenzae (HK-NTHi) on days 7 and 21. One day after the last exposure to CS, mice were sacrificed and lung inflammation and mechanics, emphysematous changes, and goblet cell metaplasia were assessed. Mice exposed to CS or HK-NTHi alone or room air served as controls. To determine the susceptibility to viral infections, we also challenged these mice with rhinovirus (RV).

Results: Unlike mice exposed to CS or HK-NTHi alone, animals exposed to CS/HK-NTHi developed emphysema, lung inflammation and goblet cell metaplasia in both large and small airways. CS/HK-NTHi-exposed mice also expressed increased levels of mucin genes and cytokines compared to mice in other groups. CS/HK-NTHi-exposed mice infected with RV demonstrated increased viral persistence, sustained neutrophilia, and further increments in mucin gene and chemokine expression compared to other groups.

Conclusions: These findings indicate that in addition to CS, bacteria may also contribute to development of COPD, particularly changes in airways. Mice exposed to CS/HK-NTHi are also more susceptible to subsequent viral infection than mice exposed to either CS or HK-NTHi alone.

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Morphometry and lung mechanics. (A) Lungs of mice exposed to RA, CS, HK-NTHi or CS/HK-NTHi were inflated to an identical pressure, processed for paraffin embedding and sections at different depth were stained with H & E. The diameters of the air spaces were measured in at least 10 random fields per slide.. Mice were anesthetized and dynamic compliance (B) and elastance (C) and pressure-volume relationships (D) were measured using Flexivent system. Data in A to C represent median with range calculated from 5 to 6 mice per group (* different from RA-exposed mice, p ≤ 0.05, ANOVA on ranks; # different from RA/HK-NTHi-exposed mice, p ≤ 0.05, ANOVA on ranks; † different from CS-exposed mice, p ≤ 0.05, ANOVA on ranks).
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Figure 3: Morphometry and lung mechanics. (A) Lungs of mice exposed to RA, CS, HK-NTHi or CS/HK-NTHi were inflated to an identical pressure, processed for paraffin embedding and sections at different depth were stained with H & E. The diameters of the air spaces were measured in at least 10 random fields per slide.. Mice were anesthetized and dynamic compliance (B) and elastance (C) and pressure-volume relationships (D) were measured using Flexivent system. Data in A to C represent median with range calculated from 5 to 6 mice per group (* different from RA-exposed mice, p ≤ 0.05, ANOVA on ranks; # different from RA/HK-NTHi-exposed mice, p ≤ 0.05, ANOVA on ranks; † different from CS-exposed mice, p ≤ 0.05, ANOVA on ranks).

Mentions: Morphometric analysis was performed to determine the mean airspace chord length. Compared to RA-exposed mice both CS- and CS/HK-NTHi-exposed mice showed small but significant increases in chord length (RA vs CS, p = 0.045; RA vs CS/HK-NTHi, p = 0.002) (Figure 3A), but mice exposed to HK-NTHi did not. The changes in chord length in mice exposed to combination of CS and HK-NTHi were higher than in mice exposed to CS alone (p = 0.031).


Combined exposure to cigarette smoke and nontypeable Haemophilus influenzae drives development of a COPD phenotype in mice.

Ganesan S, Comstock AT, Kinker B, Mancuso P, Beck JM, Sajjan US - Respir. Res. (2014)

Morphometry and lung mechanics. (A) Lungs of mice exposed to RA, CS, HK-NTHi or CS/HK-NTHi were inflated to an identical pressure, processed for paraffin embedding and sections at different depth were stained with H & E. The diameters of the air spaces were measured in at least 10 random fields per slide.. Mice were anesthetized and dynamic compliance (B) and elastance (C) and pressure-volume relationships (D) were measured using Flexivent system. Data in A to C represent median with range calculated from 5 to 6 mice per group (* different from RA-exposed mice, p ≤ 0.05, ANOVA on ranks; # different from RA/HK-NTHi-exposed mice, p ≤ 0.05, ANOVA on ranks; † different from CS-exposed mice, p ≤ 0.05, ANOVA on ranks).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3926338&req=5

Figure 3: Morphometry and lung mechanics. (A) Lungs of mice exposed to RA, CS, HK-NTHi or CS/HK-NTHi were inflated to an identical pressure, processed for paraffin embedding and sections at different depth were stained with H & E. The diameters of the air spaces were measured in at least 10 random fields per slide.. Mice were anesthetized and dynamic compliance (B) and elastance (C) and pressure-volume relationships (D) were measured using Flexivent system. Data in A to C represent median with range calculated from 5 to 6 mice per group (* different from RA-exposed mice, p ≤ 0.05, ANOVA on ranks; # different from RA/HK-NTHi-exposed mice, p ≤ 0.05, ANOVA on ranks; † different from CS-exposed mice, p ≤ 0.05, ANOVA on ranks).
Mentions: Morphometric analysis was performed to determine the mean airspace chord length. Compared to RA-exposed mice both CS- and CS/HK-NTHi-exposed mice showed small but significant increases in chord length (RA vs CS, p = 0.045; RA vs CS/HK-NTHi, p = 0.002) (Figure 3A), but mice exposed to HK-NTHi did not. The changes in chord length in mice exposed to combination of CS and HK-NTHi were higher than in mice exposed to CS alone (p = 0.031).

Bottom Line: CS/HK-NTHi-exposed mice also expressed increased levels of mucin genes and cytokines compared to mice in other groups.CS/HK-NTHi-exposed mice infected with RV demonstrated increased viral persistence, sustained neutrophilia, and further increments in mucin gene and chemokine expression compared to other groups.These findings indicate that in addition to CS, bacteria may also contribute to development of COPD, particularly changes in airways.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan, 1150 W, Medical Center Dr,, Ann Arbor, MI 48109-5688, USA. usajjan@umich.edu.

ABSTRACT

Background: Cigarette smoke (CS) is the major etiologic factor of chronic obstructive pulmonary disease (COPD). CS-exposed mice develop emphysema and mild pulmonary inflammation but no airway obstruction, which is also a prominent feature of COPD. Therefore, CS may interact with other factors, particularly respiratory infections, in the pathogenesis of airway remodeling in COPD.

Methods: C57BL/6 mice were exposed to CS for 2 h a day, 5 days a week for 8 weeks. Mice were also exposed to heat-killed non-typeable H. influenzae (HK-NTHi) on days 7 and 21. One day after the last exposure to CS, mice were sacrificed and lung inflammation and mechanics, emphysematous changes, and goblet cell metaplasia were assessed. Mice exposed to CS or HK-NTHi alone or room air served as controls. To determine the susceptibility to viral infections, we also challenged these mice with rhinovirus (RV).

Results: Unlike mice exposed to CS or HK-NTHi alone, animals exposed to CS/HK-NTHi developed emphysema, lung inflammation and goblet cell metaplasia in both large and small airways. CS/HK-NTHi-exposed mice also expressed increased levels of mucin genes and cytokines compared to mice in other groups. CS/HK-NTHi-exposed mice infected with RV demonstrated increased viral persistence, sustained neutrophilia, and further increments in mucin gene and chemokine expression compared to other groups.

Conclusions: These findings indicate that in addition to CS, bacteria may also contribute to development of COPD, particularly changes in airways. Mice exposed to CS/HK-NTHi are also more susceptible to subsequent viral infection than mice exposed to either CS or HK-NTHi alone.

Show MeSH
Related in: MedlinePlus