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Contribution of mucus concentration and secreted mucins Muc5ac and Muc5b to the pathogenesis of muco-obstructive lung disease
by
Burns, K.A.
, Grubb, B.R.
, Wilkinson, K.J.
, Evans, C.M.
, O'Neal, W.K.
, Livraghi-Butrico, A.
, Boucher, R.C.
, Volmer, A.S.
in
631/250/347
/ 692/420/256
/ 692/699/1785
/ 692/700/565
/ Airway Obstruction - genetics
/ Allergology
/ Animals
/ Antibodies
/ article-report
/ Biomedical and Life Sciences
/ Biomedicine
/ Bronchi - pathology
/ Bronchi - physiology
/ Bronchitis, Chronic - immunology
/ Cystic Fibrosis - immunology
/ Epithelial Sodium Channels - genetics
/ Gastroenterology
/ Homeostasis
/ Humans
/ Immunology
/ Kartagener Syndrome - immunology
/ Mice
/ Mice, Inbred C57BL
/ Mice, Knockout
/ Mice, Transgenic
/ Mucin 5AC - genetics
/ Mucin 5AC - metabolism
/ Mucin-5B - genetics
/ Mucin-5B - metabolism
/ Mucociliary Clearance - genetics
/ Smoking - adverse effects
2017
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Contribution of mucus concentration and secreted mucins Muc5ac and Muc5b to the pathogenesis of muco-obstructive lung disease
by
Burns, K.A.
, Grubb, B.R.
, Wilkinson, K.J.
, Evans, C.M.
, O'Neal, W.K.
, Livraghi-Butrico, A.
, Boucher, R.C.
, Volmer, A.S.
in
631/250/347
/ 692/420/256
/ 692/699/1785
/ 692/700/565
/ Airway Obstruction - genetics
/ Allergology
/ Animals
/ Antibodies
/ article-report
/ Biomedical and Life Sciences
/ Biomedicine
/ Bronchi - pathology
/ Bronchi - physiology
/ Bronchitis, Chronic - immunology
/ Cystic Fibrosis - immunology
/ Epithelial Sodium Channels - genetics
/ Gastroenterology
/ Homeostasis
/ Humans
/ Immunology
/ Kartagener Syndrome - immunology
/ Mice
/ Mice, Inbred C57BL
/ Mice, Knockout
/ Mice, Transgenic
/ Mucin 5AC - genetics
/ Mucin 5AC - metabolism
/ Mucin-5B - genetics
/ Mucin-5B - metabolism
/ Mucociliary Clearance - genetics
/ Smoking - adverse effects
2017
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Contribution of mucus concentration and secreted mucins Muc5ac and Muc5b to the pathogenesis of muco-obstructive lung disease
by
Burns, K.A.
, Grubb, B.R.
, Wilkinson, K.J.
, Evans, C.M.
, O'Neal, W.K.
, Livraghi-Butrico, A.
, Boucher, R.C.
, Volmer, A.S.
in
631/250/347
/ 692/420/256
/ 692/699/1785
/ 692/700/565
/ Airway Obstruction - genetics
/ Allergology
/ Animals
/ Antibodies
/ article-report
/ Biomedical and Life Sciences
/ Biomedicine
/ Bronchi - pathology
/ Bronchi - physiology
/ Bronchitis, Chronic - immunology
/ Cystic Fibrosis - immunology
/ Epithelial Sodium Channels - genetics
/ Gastroenterology
/ Homeostasis
/ Humans
/ Immunology
/ Kartagener Syndrome - immunology
/ Mice
/ Mice, Inbred C57BL
/ Mice, Knockout
/ Mice, Transgenic
/ Mucin 5AC - genetics
/ Mucin 5AC - metabolism
/ Mucin-5B - genetics
/ Mucin-5B - metabolism
/ Mucociliary Clearance - genetics
/ Smoking - adverse effects
2017
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Contribution of mucus concentration and secreted mucins Muc5ac and Muc5b to the pathogenesis of muco-obstructive lung disease
Journal Article
Contribution of mucus concentration and secreted mucins Muc5ac and Muc5b to the pathogenesis of muco-obstructive lung disease
2017
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Overview
Airway diseases, including cigarette smoke-induced chronic bronchitis, cystic fibrosis, and primary ciliary dyskinesia are associated with decreased mucociliary clearance (MCC). However, it is not known whether a simple reduction in MCC or concentration-dependent mucus adhesion to airway surfaces dominates disease pathogenesis or whether decreasing the concentration of secreted mucins may be therapeutic. To address these questions, Scnn1b-Tg mice, which exhibit airway mucus dehydration/adhesion, were compared and crossed with Muc5b- and Muc5ac-deficient mice. Absence of Muc5b caused a 90% reduction in MCC, whereas Scnn1b-Tg mice exhibited an ∼50% reduction. However, the degree of MCC reduction did not correlate with bronchitic airway pathology, which was observed only in Scnn1b-Tg mice. Ablation of Muc5b significantly reduced the extent of mucus plugging in Scnn1b-Tg mice. However, complete absence of Muc5b in Scnn1b-Tg mice was associated with increased airway inflammation, suggesting that Muc5b is required to maintain immune homeostasis. Loss of Muc5ac had few phenotypic consequences in Scnn1b-Tg mice. These data suggest that: (i) mucus hyperconcentration dominates over MCC reduction alone to produce bronchitic airway pathology; (ii) Muc5b is the dominant contributor to the Scnn1b-Tg phenotype; and (iii) therapies that limit mucin secretion may reduce plugging, but complete Muc5b removal from airway surfaces may be detrimental.
Publisher
Elsevier Inc,Nature Publishing Group US,Elsevier Limited
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