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Attached stratified mucus separates bacteria from the epithelial cells in COPD lungs
Joan Antoni Fernández-Blanco, Dalia Fakih, Liisa Arike, Ana M. Rodríguez-Piñeiro, Beatriz Martínez-Abad, Elin Skansebo, Sonya Jackson, James Root, Dave Singh, Christopher McCrae, Christopher M. Evans, Annika Åstrand, Anna Ermund, Gunnar C. Hansson
Joan Antoni Fernández-Blanco, Dalia Fakih, Liisa Arike, Ana M. Rodríguez-Piñeiro, Beatriz Martínez-Abad, Elin Skansebo, Sonya Jackson, James Root, Dave Singh, Christopher McCrae, Christopher M. Evans, Annika Åstrand, Anna Ermund, Gunnar C. Hansson
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Research Article Pulmonology

Attached stratified mucus separates bacteria from the epithelial cells in COPD lungs

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Abstract

The respiratory tract is normally kept essentially free of bacteria by cilia-mediated mucus transport, but in chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF), bacteria and mucus accumulates instead. To address the mechanisms behind the mucus accumulation, the proteome of bronchoalveolar lavages from COPD patients and mucus collected in an elastase-induced mouse model of COPD was analyzed, revealing similarities with each other and with the protein content in colonic mucus. Moreover, stratified laminated sheets of mucus were observed in airways from patients with CF and COPD and in elastase-exposed mice. On the other hand, the mucus accumulation in the elastase model was reduced in Muc5b-KO mice. While mucus plugs were removed from airways by washing with hypertonic saline in the elastase model, mucus remained adherent to epithelial cells. Bacteria were trapped on this mucus, whereas, in non–elastase-treated mice, bacteria were found on the epithelial cells. We propose that the adherence of mucus to epithelial cells observed in CF, COPD, and the elastase-induced mouse model of COPD separates bacteria from the surface cells and, thus, protects the respiratory epithelium.

Authors

Joan Antoni Fernández-Blanco, Dalia Fakih, Liisa Arike, Ana M. Rodríguez-Piñeiro, Beatriz Martínez-Abad, Elin Skansebo, Sonya Jackson, James Root, Dave Singh, Christopher McCrae, Christopher M. Evans, Annika Åstrand, Anna Ermund, Gunnar C. Hansson

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Figure 2

Mice exposed to elastase (PPE) show goblet cell hyperplasia/metaplasia and mucus accumulation in the airways.

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Mice exposed to elastase (PPE) show goblet cell hyperplasia/metaplasia a...
(A) Alcian blue/Periodic acid-Schiff–stained (AB/PAS-stained) tissue section of mice airways exposed i.n. to saline (vehicle). (B) AB/PAS-stained tissue section of mice airways exposed i.n. to elastase (PPE), showing a marked increase in AB/PAS-positive cells. Representative images of 4–5 animals/group. Scale bar: 100 μm (left panels) or 33 μm (right panels). (C and D) High- and low-magnification images of lungs from mice exposed to saline or elastase (PPE). Scale bar: 100 μm. (E) Paraffin sections stained with H&E revealed few immune cells around intrapulmonary airways and intact alveoli from saline-instilled mice. Mild perivascular and peribronchiolar lymphocytic infiltration and damaged alveoli were detected in PPE-challenged mice. Scale bar: 100 μm. (F) Airway obstruction presented by measuring the percentage of airway luminal area containing AB/PAS-stained material in 1 entire lung section per animal; n = 4–9 animals/group, median ± IQR, saline vs. PPE (**P = 0.001), inactivated PPE vs. PPE (*P = 0.01), Kruskal-Wallis test with Dunn’s multiple comparisons test. (G) Differential white blood cell counts in BALF of vehicle- and PPE-exposed mice; n = 9–17 animals/group, data presented as median ± IQR, neutrophils (***P = 0.0008), eosinophils (****P < 0.0001), macrophages (***P = 0.0005), and lymphocytes (****P < 0.0001), Mann-Whitney U test.

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