Strategies for measuring airway mucus and mucins

Atanasova, Kalina R.; Reznikov, Leah R.

doi:10.1186/s12931-019-1239-z

Cited by 50 publications

(50 citation statements)

References 150 publications

(243 reference statements)

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“…However, as mentioned, the extent of mucus sheet formation was greater, whereas in the present study the differences in mucus sheet formation were mild. Thus, these findings suggest that additional factors, such as robust inflammation and/or altered concentrations of mucins (Evans, Kim, Tuvim, & Dickey, 2009; Roy et al., 2014), are required for mucociliary transport defects (Atanasova & Reznikov, 2019). Indeed, mucociliary transport defects in CF pigs were prominent upon methacholine stimulation and involved a failure of mucus detachment from the gland (Hoegger et al., 2014).…”

Section: Discussionmentioning

confidence: 98%

Airway cholinergic history modifies mucus secretion properties to subsequent cholinergic challenge in diminished chloride and bicarbonate conditions

Liao

Collins

Guevara

et al. 2020

Experimental Physiology

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Viral infections precipitate exacerbations in many airway diseases, including asthma and cystic fibrosis. Although viral infections increase cholinergic transmission, few studies have examined how cholinergic history modifies subsequent cholinergic responses in the airway. In our previous work, we found that airway resistance in response to a second cholinergic challenge was increased in young pigs with a history of airway cholinergic stimulation. Given that mucus secretion is regulated by the cholinergic nervous system and that abnormal airway mucus contributes to exacerbations of airway disease, we hypothesized that prior cholinergic challenge would also modify subsequent mucus responses to a secondary cholinergic challenge. Using our established cholinergic challenge-rechallenge model in pigs, we atomized the cholinergic agonist bethanechol or saline control to pig airways. Forty-eight hours later, we removed tracheas and measured mucus secretion properties in response to a second cholinergic stimulation. The second cholinergic stimulation was conducted in conditions of diminished chloride and bicarbonate transport to mimic a cystic fibrosis-like environment. In pigs previously challenged with bethanechol, a second cholinergic stimulation produced a mild increase in sheet-like mucus films; these films were scarcely observed in animals originally challenged with saline control. The subtle increase in mucus films was not associated with changes in mucociliary transport. These data suggest that prior cholinergic history might modify mucus secretion characteristics with subsequent stimulation in certain environmental conditions or disease states. Such modifications and/or more repetitive stimulation might lead to retention of mucus on the airway surface, thereby potentiating exacerbations of airway disease.

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Section: Discussionmentioning

confidence: 98%

Airway cholinergic history modifies mucus secretion properties to subsequent cholinergic challenge in diminished chloride and bicarbonate conditions

Liao

Collins

Guevara

et al. 2020

Experimental Physiology

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“…Although bethanechol stimulation was associated with mucus sheet formation and diminished fluid secretion and Cltransport, no decrements in mucociliary transport were observed. This finding suggests that additional factors, such as robust inflammation and/or altered concentrations of mucins [39,40], are required for mucociliary transport defects [41]. Another consideration is that submucosal gland fluid secretion and/or augmentation of ciliary beat frequency [42] compensate for the diminished fluid secretion mediated by surface epithelia, masking the detection of a defect.…”

Section: Discussionmentioning

confidence: 99%

Durable Changes to Airway Mucus and Fluid Secretion Following Cholinergic Challenge

Liao

Collins

Guevara

et al. 2020

Preprint

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Number of Tables: 1Conflict of interest statement: None declared. AbstractPurpose: Mucus abnormalities are central to the pathophysiology of several chronic airway diseases. Mucus secretion and clearance are regulated, in part, by cholinergic innervation.Prolonged cholinergic stimulation may contribute to mucus abnormalities in disease. Thus, we tested the hypothesis that prolonged cholinergic stimulation gives rise to lasting mucus abnormalities in airways. Methods:We delivered aerosolized bethanechol, a cholinergic agonist, to pig airways. Fortyeight hours later, we measured mucus secretion and mucociliary transport in tracheal segments ex vivo. Tracheal and bronchoalveolar lavage concentrations of the major secreted mucus glycoproteins, mucin5B (MUC5B) or mucin5AC (MUC5AC), were measured with ELISA and antibody labeling. Pig airway epithelia were cultured at the air-liquid interface and treated with bethanechol for forty-eight hours. Stimulated fluid secretion was measured with reflected microscopy and Ussing chambers were used to measure ion transport.Results: Airways from bethanechol-challenged pigs exhibited sheet-like mucus films, which were not associated with a greater abundance of MUC5AC or MUC5B. Epithelia treated with bethanechol had diminished fluid secretion and decreased Cltransport. However, mucus and fluid alterations were not associated with impaired mucociliary transport. Conclusions:These data suggest that cholinergic transmission induces sustained alterations in airway mucus properties. Such defects might compound and/or contribute to persistent mucus phenotypes found after the resolution of airway inflammation.

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“…They created the term "ionocytes" due to the cell's likeness to ionocytes in charge of regulating ion transport and hydration in the fish gills and frog skin. In the airway, ASL consists of two main layers: 1) the apical layer consisting of a water-based polymeric mucus, and 2) a periciliary layer (PCL) that bathes the epithelium (Atanasova and Reznikov, 2019). Normal mucus is made of 97% water and 3% proteins, lipids, and salt.…”

Section: Mucus Alterationmentioning

confidence: 99%

Novel Anti-Inflammatory Approaches for Cystic Fibrosis Lung Disease: Identification of Molecular Targets and Design of Innovative Therapies

Mitri

Bardin

et al. 2020

Front. Pharmacol.

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Cystic fibrosis (CF) is the most common genetic disorder among Caucasians, estimated to affect more than 70,000 people in the world. Severe and persistent bronchial inflammation and chronic bacterial infection, along with airway mucus obstruction, are hallmarks of CF lung disease and participate in its progression. Anti-inflammatory therapies are, therefore, of particular interest for CF lung disease. Furthermore, a better understanding of the molecular mechanisms involved in airway infection and inflammation in CF has led to the development of new therapeutic approaches that are currently under evaluation by clinical trials. These new strategies dedicated to CF inflammation are designed to treat different dysregulated aspects such as oxidative stress, cytokine secretion, and the targeting of dysregulated pathways. In this review, we summarize the current understanding of the cellular and molecular mechanisms that contribute to abnormal lung inflammation in CF, as well as the new anti-inflammatory strategies proposed to CF patients by exploring novel molecular targets and novel drug approaches.

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Strategies for measuring airway mucus and mucins

Cited by 50 publications

References 150 publications

Airway cholinergic history modifies mucus secretion properties to subsequent cholinergic challenge in diminished chloride and bicarbonate conditions

Airway cholinergic history modifies mucus secretion properties to subsequent cholinergic challenge in diminished chloride and bicarbonate conditions

Durable Changes to Airway Mucus and Fluid Secretion Following Cholinergic Challenge

Novel Anti-Inflammatory Approaches for Cystic Fibrosis Lung Disease: Identification of Molecular Targets and Design of Innovative Therapies

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