CFTR involvement in chloride, bicarbonate, and liquid secretion by airway submucosal glands

Ballard, Stephen T.; Trout, Laura; Bebök, Zsuzsa; Sorscher, Eric J.; Crews, Angela

doi:10.1152/ajplung.1999.277.4.l694

Cited by 119 publications

(163 citation statements)

References 13 publications

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“…Gland secretion in response to pharmacological mediators has been extensively studied in the tracheas and isolated airways of pigs Inglis, Corboz et al 1998;Trout, Gatzy et al 1998;Trout, King et al 1998;Ballard, Trout et al 1999;Crews, Taylor et al 2001;Trout, Corboz et al 2001;Phillips, Hey et al 2003;Trout, Townsley et al 2003;Ballard and Inglis 2004;Ballard, Trout et al 2006). Control experiments establish that secretions studied in this way are virtually all from the submucosal glands.…”

Section: Airway Submucosal Glandsmentioning

confidence: 99%

Parasympathetic control of airway submucosal glands: Central reflexes and the airway intrinsic nervous system

Wine

2007

Autonomic Neuroscience

103

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Airway submucosal glands produce the mucus that lines the upper airways to protect them against insults. This review summarizes evidence for two forms of gland secretion, and hypothesizes that each is mediated by different but partially overlapping neural pathways. Airway innate defense comprises low level gland secretion, mucociliary clearance and surveillance by airway-resident phagocytes to keep the airways sterile in spite of nearly continuous inhalation of low levels of pathogens. Gland secretion serving innate defense is hypothesized to be under the control of intrinsic (peripheral) airway neurons and local reflexes, and these may depend disproportionately on noncholinergic mechanisms, with most secretion being produced by VIP and tachykinins. In the genetic disease cystic fibrosis, airway glands no longer secrete in response to VIP alone and fail to show the synergy between VIP, tachykinins and ACh that is observed in normal glands. The consequent crippling of the submucosal gland contribution to innate defense may be one reason that cystic fibrosis airways are infected by mucus-resident bacteria and fungi that are routinely cleared from normal airways. By contrast, the acute (emergency) airway defense reflex is centrally mediated by vagal pathways, is primarily cholinergic, and stimulates copious volumes of gland mucus in response to acute, intense challenges to the airways, such as those produced by very vigorous exercise or aspiration of foreign material. In cystic fibrosis, the acute airway defense reflex can still stimulate the glands to secrete large amounts of mucus, although its properties are altered. Importantly, treatments that recruit components of the acute reflex, such as inhalation of hypertonic saline, are beneficial in treating cystic fibrosis airway disease. The situation for recipients of lung transplants is the reverse; transplanted airways retain the airway intrinsic nervous system but lose centrally mediated reflexes. The consequences of this for gland secretion and airway defense are poorly understood, but it is possible that interventions to modify submucosal gland secretion in transplanted lungs might have therapeutic consequences.

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Section: Airway Submucosal Glandsmentioning

confidence: 99%

Parasympathetic control of airway submucosal glands: Central reflexes and the airway intrinsic nervous system

Wine

2007

Autonomic Neuroscience

103

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“…The defective gene was identified in 1989 [3][4][5] and shown to encode the cystic fibrosis trans-membrane conductance regulator protein (CFTR). CFTR is a cyclic AMP-regulated anion channel with greatest selectivity for chloride, and bicarbonate [6][7][8]. Furthermore, CFTR regulates sodium transport across epithelial membranes through interactions with the epithelial sodium channel ENaC [9], and facilitates the trans-membrane export of the small organic anionic peptide glutathione [10].…”

Section: Introductionmentioning

confidence: 99%

Antioxidants in cystic fibrosis☆Conclusions from the CF Antioxidant Workshop, Bethesda, Maryland, November 11-12, 2003

Cantin

White

Cross

et al. 2007

Free Radical Biology and Medicine

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Although great strides are being made in the care of individuals with cystic fibrosis (CF), this condition remains the most common fatal hereditary disease in North America. Numerous links exist between progression of CF lung disease and oxidative stress. The defect in CF is the loss of function of the transmembrane conductance regulator (CFTR) protein; recent evidence that CFTR expression and function are modulated by oxidative stress suggests that the loss may result in a poor adaptive response to oxidants. Pancreatic insufficiency in CF also increases susceptibility to deficiencies in lipophilic antioxidants. Finally the airway infection and inflammatory processes in the CF lung are potential sources of oxidants that can affect normal airway physiology and contribute to the mechanisms causing characteristic changes associated with bronchiectasis and loss of lung function. These multiple abnormalities in the oxidant/antioxidant balance raise several possibilities for therapeutic interventions that must be carefully assessed. IntroductionCystic fibrosis (CF) is the most common fatal disease caused by a single gene defect in Europe and North America [1,2]. The defective gene was identified in 1989 [3][4][5] and shown to encode the cystic fibrosis trans-membrane conductance regulator protein (CFTR). CFTR is a cyclic AMP-regulated anion channel with greatest selectivity for chloride, and bicarbonate [6][7][8]. Furthermore, CFTR regulates sodium transport across epithelial membranes through interactions with the epithelial sodium channel ENaC [9], and facilitates the trans-membrane export of the small organic anionic peptide glutathione [10]. The expression of CFTR is located in the apical membrane of epithelial cells that line mucous membranes and submucosal glands ☆ A list of participants may be found in the Acknowledgments.

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“…is defective gene encodes the cystic brosis trans-membrane conductance regulator protein or CFTR [4][5][6]. New therapies addressing this defect are being tested in clinical trials [7,8]; however, quantifying clinical bene ts remains a major challenge.…”

mentioning

confidence: 99%

Plasma biomarkers and cystic fibrosis lung disease

Cantin

Bilodeau²,

Larivée³

et al. 2012

CIM

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Plasma biomarkers and cystic brosis lung disease AbstractPurpose: e purpose of this study was to determine whether plasma biomarkers re ect changes in lung function and respiratory exacerbations associated with CF lung disease.Methods: Plasma human leukocyte elastase/alpha1 antitrypsin complex (pHLE complex) values were measured in 28 adult CF patients and 47 healthy volunteers and correlated with forced expiratory volume (FEV1) and forced vital capacity (FVC). pHLE complexes were studied during respiratory exacerbations and a er antibiotic therapy. Plasma cytokines and sialic acid were also measured.Results: pHLE complexes were increased in CF patients (p < 0.01), were inversely correlated with FEV1 (r = 0.71) and FVC (r = 0.67) and returned to normal levels a er intravenous antibiotics (p < 0.001). Plasma cytokines did not correlate with lung function. Total sialic acid increased during CF respiratory exacerbations and decreased a er antibiotic therapy.Conclusion: Plasma sialic acid and pHLE complexes re ect clinically meaningful changes in CF lung disease. In contrast, plasma cytokine levels did not correlate with lung function.

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CFTR involvement in chloride, bicarbonate, and liquid secretion by airway submucosal glands

Cited by 119 publications

References 13 publications

Parasympathetic control of airway submucosal glands: Central reflexes and the airway intrinsic nervous system

Parasympathetic control of airway submucosal glands: Central reflexes and the airway intrinsic nervous system

Antioxidants in cystic fibrosis☆Conclusions from the CF Antioxidant Workshop, Bethesda, Maryland, November 11-12, 2003

Plasma biomarkers and cystic fibrosis lung disease

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