Bioelectric properties and ion flow across excised human bronchi

Knowles, Michael R.; Murray, Gordon F.; Shallal, J. A.; Askin, Frederic B.; Ranga, V.; Gatzy, J. T.; Boucher, Richard C.

doi:10.1152/jappl.1984.56.4.868

Cited by 158 publications

(73 citation statements)

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“…Nasal potential difference measurements have been used in neonates (5,17,24) and in adults with cystic fibrosis (25) as a proxy measure to examine airway ion transport throughout the respiratory epithelium. The epithelium along the floor of the nose of neonates is formed by cuboidal, ciliated cells, which are very similar morphologically and in their ion transport characteristics to those found in the lower respiratory tract (26). The PD measured reflects the sum of ion transport processes across the epithelium.…”

Section: Discussionmentioning

confidence: 99%

Electrical Potential Difference Across the Nasal Epithelium Is Reduced in Premature Infants With Chronic Lung Disease but Is Not Associated With Lower Airway Inflammation

et al. 2007

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Airway liquid content and insufficient absorptive airway ion transport at birth are potentially important factors in the development and severity of neonatal respiratory disease. The role of deficient absorptive airway ion transport in the development of chronic lung disease of prematurity is unknown. Additionally, lung inflammatory mediators modulate airway ion transport. Their effect on preterm lung ion transport and absorptive capacity is not established. We performed serial nasal potential difference studies and broncho-alveolar lavage in preterm infants born less than 30 wk postmenstrual age over the first four postnatal weeks. Our study aims were to: 1) compare nasal potential difference between preterm infants developing chronic lung disease and babies of similar gestation who do not; and 2) examine for an association between airway inflammation and ion transport parameters. We found that potential difference across the nasal epithelium increased with gestation, remained low and unchanged in infants developing chronic lung disease over the first four postnatal weeks, was significantly lower at four weeks in chronic lung disease infants, and was not associated with lower airway inflammation at any time point. We conclude that infants with chronic lung disease postnatally have a persistently reduced absorptive airway ion transport capacity. (Pediatr Res 61: 77-82, 2007) T he incidence of chronic lung disease of prematurity (CLD) in very preterm infants has not changed significantly over the last decade despite the routine administration of antenatal steroids and postnatal exogenous surfactant (1,2).A greater residual airway liquid content resulting from incompletely developed absorptive airway ion transport processes at birth is a potentially important factor in the pathogenesis and severity of the neonatal respiratory distress syndrome (RDS) (3-5). Compared with preterm babies without neonatal lung disease, those with RDS have an increased lung liquid content (6,7).Lung inflammation is present in preterm infants with RDS (8,9). Those who develop CLD experience a persistent and greater lung inflammatory response (10,11).Recent studies have demonstrated that inflammatory mediators influence airway ion transport processes (12-16). However, in vitro studies have given conflicting results with respect to the effect of cytokines on airway ion transport processes. Interleukin (IL)-4 and interferon-␥ inhibit the amiloride sensitive epithelial sodium channel (ENaC) (12,13) in polarized cultured human bronchial epithelial cells whereas tumor necrosis factor (TNF)-␣ was not found to modulate ion transport (13). In vivo experiments have demonstrated a TNF-␣ (14), IL-1␤ (15) and TGF-␣ (16) mediated increase in lung liquid absorption. These studies were conducted with single cytokines in models of mature lung epithelium. There are no data on the impact of cytokines on the airway ion transport processes of the human newborn lung in vivo.The aim of this study was to examine in vivo the association between cytoki...

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Section: Discussionmentioning

confidence: 99%

Electrical Potential Difference Across the Nasal Epithelium Is Reduced in Premature Infants With Chronic Lung Disease but Is Not Associated With Lower Airway Inflammation

et al. 2007

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“…Under unstimulated conditions, the main form of transepithelial solute transport across human airway epithelia is active absorption of Na + [17][18][19]. Active secretion of Cl -can be induced transiently by several mediators [19].…”

Section: Ion and Fluid Transport Across Surface Epitheliummentioning

confidence: 99%

Regulation of depth and composition of airway surface liquid

Widdicombe¹,

Bastacky²,

Wu³

et al. 1997

Eur Respir J

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R Re eg gu ul la at ti io on n o of f d de ep pt th h a an nd d c co om mp po os si it ti io on n o of f a ai ir rw wa ay y s su ur rf fa ac ce e l li iq qu ui id dThe airways are lined with a film of fluid, which is 5-20 µm deep in healthy individuals. This fluid is believed to consist of two phases [1]. A watery fluid of low viscosity, the "periciliary sol" surrounds the cilia. Above this lies a viscous mucous gel. The cilia are able to beat in the sol. Their tips contact the underside of the mucous blanket and propel it towards the mouth. This system of "mucociliary clearance" serves to remove particles trapped in the mucous gel. The concept of two layers of airway surface liquid (ASL) has been supported by a variety of microscopy studies [2][3][4][5] (fig. 1).Factors influencing the liquid content of sol and gel have been identified but their relative contributions are imperfectly understood. Water will move into the airway lumen in response to active Cl -secretion across the epithelia of the tracheal surface and of submucosal glands. Active absorption of Na + across the surface epithelium serves to remove liquid. These active ion transport processes move liquid by generating local osmotic gradients across the epithelium [6]. Hydrostatic pressure gradients across the epithelium, and differences in osmotic pressure between the media bathing the epithelium's two surfaces, will also influence the net movement of liquid into or out of the lumen. Evaporation is an important factor in the upper airways. Finally, forces of surface tension generated by the closely packed cilia SERIES "AIRWAY MUCUS" Edited by P.K. JefferyNumber 6 in this Series may serve to hold liquid in the airway lumen [7]. These factors are considered in turn below. Additionally, we describe recent experiments in which we have used lowtemperature scanning electron microscope (LT-SEM) to determine the depth and composition of the airway surface liquid (ASL). Gland secretionThe adult human trachea has about 10 submucosal gland openings per mm 2 of airway surface [8]. It is unknown how the structure and numbers of glands change down the airways, except that bronchi have glands, whereas bronchioles do not [9]. In each gland, a ciliated duct leads from the airway surface to an expanded collecting duct into which empty ~10 secretory tubules, each with multiple branches ending in closed acini [10]. The acini are lined by serous cells, the tubules by mucous cells [11]. It is believed that the serous cells secrete fluid which serves to flush out mucins released by the more proximal mucous cells [12]. Consistent with this hypothesis, gland serous cells contain much the highest levels of the cystic fibrosis transmembrane conductance regulator of any cell type in the airways [13] Respir J 1997; 10: 1914-1917

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“…The present study was initiated with two goals: (a) to compare the rate ofNa' absorption across excised and short-circuited airway epithelia from a large number of CF patients, with that oftissue obtained from normal and disease control subjects; and (b) to test in CF respiratory epithelia the effects of agents, e.g., beta adrenergic agonists, that stimulate chloride secretion in normal respiratory epithelia (9)(10)(11). Because these agents are thought to work by changing cell cAMP concentrations (10-1 1), we also investigated the effects of beta adrenergic agonists on the rate of cAMP production in tissue biopsies of CF and normal nasal epithelia.…”

Section: Introductionmentioning

confidence: 99%

Na+ transport in cystic fibrosis respiratory epithelia. Abnormal basal rate and response to adenylate cyclase activation.

Boucher¹,

Stutts²,

Knowles³

et al. 1986

J. Clin. Invest.

532

238

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The transepithelial potential difference (PD) of cystic fibrosis (CF) airway epithelium is abnormally raised and the Cl-permeability is low. We studied the contribution of active Na' absorption to the PD and attempted to increase the Cl-permeability of CF epithelia. Nasal epithelia from CF and control subjects were mounted in Ussing chambers and were short-circuited. The basal rate of Na' absorption was raised in CF polyps compared with control tissues. Whereas beta agonists induced Cl-secretion in normal and atopic epithelia, beta agonists further increased the rate of Na' absorption in CF epithelia without inducing Clsecretion. This unusual effect is not due to an abnormal CF beta receptor because similar effects were induced by forskolin, and because cAMP production was similar in normal and CF epithelia. We conclude that CF airway epithelia absorb Na' at an accelerated rate. The abnormal response to beta agonists may reflect a primary abnormality in a cAMP-modulated path, or a normal cAMP-modulated process in a Cl-impermeable epithelial cell.

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Bioelectric properties and ion flow across excised human bronchi

Cited by 158 publications

References 0 publications

Electrical Potential Difference Across the Nasal Epithelium Is Reduced in Premature Infants With Chronic Lung Disease but Is Not Associated With Lower Airway Inflammation

Electrical Potential Difference Across the Nasal Epithelium Is Reduced in Premature Infants With Chronic Lung Disease but Is Not Associated With Lower Airway Inflammation

Regulation of depth and composition of airway surface liquid

Na+ transport in cystic fibrosis respiratory epithelia. Abnormal basal rate and response to adenylate cyclase activation.

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