Modification of transepithelial ion transport in human cultured bronchial epithelial cells by interferon-γ

Galietta, Luis J. V.; Folli, Chiara; Marchetti, Carla; Romanò, Luca; Carpani, Daniela; Conese, Massimo; Zegarra‐Moran, Olga

doi:10.1152/ajplung.2000.278.6.l1186

Cited by 70 publications

(80 citation statements)

References 46 publications

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“…It suppression leads to bacterial proliferation due to the absence of intracellular clearance or by epithelial ionic alterations 25,26 . Thus, reductions on INF-γ levels as observed in this study would explain the presence of bacteria or bacterial LPS in the intracellular realm.…”

Section: Discussionmentioning

confidence: 99%

Perfil de citocinas da polipose nasossinusal na Fibrose Cística comparado com indivíduos sem doenças nasossinusais

Nunes¹,

Castro²,

Silva³

et al. 2010

Braz. j. otorhinolaryngol. (Impr.)

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Section: Discussionmentioning

confidence: 99%

Perfil de citocinas da polipose nasossinusal na Fibrose Cística comparado com indivíduos sem doenças nasossinusais

Nunes¹,

Castro²,

Silva³

et al. 2010

Braz. j. otorhinolaryngol. (Impr.)

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“…Indeed, even without considering the absence of effect of 6-MP on AFC, there is little evidence that the decline in AFC on Day 2 is a consequence of the immune response to the virus. Although certain proinflammatory cytokines have been shown to modulate Na ϩ transport in vitro or in vivo (37)(38)(39)(40), analysis of BAL fluid from RSV-infected mice reveals no temporal correlation between pulmonary inflammation and inhibition of AFC. For example, whereas IFN-␥ has been shown to inhibit Na ϩ transport in vitro (38), no IFN-␥ is detectable in BAL fluid on Day 2, when AFC is most depressed, and AFC values are normal on Day 6, when BAL IFN-␥ levels are highest.…”

Section: Effect Of De Novo Nucleotide Synthesis Inhibition On Afcmentioning

confidence: 97%

Leflunomide Prevents Alveolar Fluid Clearance Inhibition by Respiratory Syncytial Virus

Davis

Lazarowski

Hickman-Davis

et al. 2006

Am J Respir Crit Care Med

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Rationale: Previously, we demonstrated that intranasal infection of BALB/c mice with respiratory syncytial virus (RSV) resulted in an early 40% reduction in alveolar fluid clearance (AFC), an effect mediated via P2Y purinergic receptors. Objectives: To confirm that RSV-induced inhibition of AFC is mediated by uridine triphosphate (UTP), and to demonstrate that inhibition of de novo pyrimidine synthesis with leflunomide prevents increased UTP release after RSV infection, and thereby also prevents inhibition of AFC by RSV. Methods: BALB/c mice were infected intranasally with RSV strain A2. AFC was measured in anesthetized, ventilated mice by instillation of 5% bovine serum albumin into the dependent lung. Some mice were pretreated with leflunomide or 6-mercaptopurine. Measurements and Main Results: RSV-mediated inhibition of AFC is associated temporally with a 20-nM increase in UTP and ATP content of bronchoalveolar lavage fluid, hypoxemia, and altered nasal potential difference. RSV-mediated nucleotide release, AFC inhibition, and physiologic sequelae thereof can be prevented by pretreatment of mice with the de novo pyrimidine synthesis inhibitor leflunomide, which is not toxic to the mice, and which does not affect RSV replication in the lungs. In contrast, pretreatment of mice with 6-mercaptopurine, an inhibitor of de novo purine synthesis, has no beneficial effect on AFC or other indicators of disease progression. Finally, RSV-mediated inhibition of AFC is prevented by volumeregulated anion channel inhibitors. Conclusion: Pyrimidine synthesis or release pathways may provide novel therapeutic targets to counter the pathophysiologic sequelae of impaired AFC in RSV disease.Keywords: ion transport; paramyxovirus infections; pneumonia, viral; pulmonary edemaThe dominant ion transport process of the alveolar epithelium is active movement of Na ϩ ions from the airspace lining fluid to the interstitium (1). This creates an osmotic gradient, causing water to follow passively. This process of alveolar fluid clearance (AFC) is crucial to efficient gas exchange. Importantly, patients with acute lung injury with intact AFC have lower morbidity and mortality than those with compromised AFC (2).Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract disease in infants and children worldwide (3), but its pathogenesis remains poorly understood. Previously, we demonstrated that infection of BALB/c mice with RSV results in reduced AFC at early time points after infection, and inferred that RSV-mediated inhibition of AFC 2 d after infection was mediated by uridine triphosphate (UTP), acting on P2Y receptors (P2YRs) on lung epithelial cells (4). The aim of the current study was to confirm the central role of UTP in mediating the inhibitory effects of RSV on AFC, and to demonstrate that pharmacologic inhibition of de novo pyrimidine synthesis with leflunomide prevents increased UTP release after RSV infection, and thereby also prevents inhibition of AFC by RSV. Furthermore, we demonstrated that blockag...

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“…Because this abnormality in nasal electric potential difference was observed within the first 12 h of life, it suggests that the absence of optimal Na ϩ transport in lung epithelia of very preterm infants may predispose to RDS and ultimately to chronic lung disease. Once lung disease is established, it is possible that inflammatory mediators may interfere with lung liquid clearance (31).…”

Section: Clinical Applicationsmentioning

confidence: 99%

Invited Review: Clearance of lung liquid during the perinatal period

Barker

Olver

2002

Journal of Applied Physiology

105

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Barker, Pierre M., and Richard E. Olver. Invited Review: Clearance of lung liquid during the perinatal period. J Appl Physiol 93: 1542-1548, 2002; 10.1152/japplphysiol.00092.2002.-At birth, the distal lung epithelium undergoes a profound phenotypic switch from secretion to absorption in the course of adaptation to air breathing. In this review, we describe the developmental regulation of key membrane transport proteins and the way in which epinephrine, oxygen, glucocorticoids, and thyroid hormones interact to bring about this crucial change in function. Evidence from molecular, transgenic, cell culture, and whole lung studies is presented, and the clinical consequences of the failure of the physiological mechanisms that underlie perinatal lung liquid absorption are discussed. lung liquid; sodium absorption; chloride secretion; epithelial sodium channel; cystic fibrosis transmembrane conductance regulator THE MECHANISMS RESPONSIBLE for lung liquid clearance during the neonatal period develop gradually during the latter part of the third trimester of pregnancy, but the phenotypic switch of the lung epithelium from net secretion to net absorption, triggered by events at birth, is sudden. Although lung liquid absorption at birth is "a performance without rehearsal," the lung may be called on for an encore in later life when these same mechanisms are activated to clear accumulated edema liquid.Many of the early studies of perinatal lung liquid clearance, which were mostly undertaken on the intact lungs of rabbits and sheep in the 1970s and 1980s, provided information in vivo on the time course and regulation of lung liquid clearance in a fully integrated physiological context. These data have been supported and augmented in the past decade by cloning of genes that regulate transepithelial ion transport [particularly the sodium pump (Na ϩ -K ϩ -ATPase) and the epithelial Na ϩ channel (ENaC)] and the use of molecular approaches that have uncovered information at a subcellular level.

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Modification of transepithelial ion transport in human cultured bronchial epithelial cells by interferon-γ

Cited by 70 publications

References 46 publications

Perfil de citocinas da polipose nasossinusal na Fibrose Cística comparado com indivíduos sem doenças nasossinusais

Perfil de citocinas da polipose nasossinusal na Fibrose Cística comparado com indivíduos sem doenças nasossinusais

Leflunomide Prevents Alveolar Fluid Clearance Inhibition by Respiratory Syncytial Virus

Invited Review: Clearance of lung liquid during the perinatal period

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