Abstract:
:Inflammatory lung disease is associated with increased epithelial permeability, but it is unclear how inflammatory cells alter epithelial permeability. Neutrophils have azurophilic granules containing elastase, cathepsin G, and defensins which are released at sites of inflammation. Experiments using whole animals and cultured cells suggest that neutrophil elastase contributes to increased epithelial permeability. Using Madin-Darby canine kidney epithelial (MDCK) monolayers, a well-described epithelial model, we asked whether neutrophil elastase directly affects epithelial permeability independent of cell death or cell detachment from the substratum. We measured permeability using 3H-mannitol. We found that neutrophil elastase increased epithelial permeability in a time- and concentration-dependent fashion. Increased permeability required prolonged (> or = 6 h) exposure to elastase, but was not associated with cytolytic injury or cell detachment. These findings are potentially relevant to the lung because we found a similar time- and concentration-dependent effect when we added elastase to cultured human bronchial epithelial cells. In MDCK cells, permeability increased without alterations in cell actin at the light microscopic level. Interestingly, elastase-induced permeability was both prevented and reversed by serum, but not by serum albumin. Complete reversal occurred if serum was added up to 16 h after adding elastase. Proteolytic activity is important in HNE-induced epithelial permeability because soy bean trypsin inhibitor completely blocks the effect and alpha 1 proteinase inhibitor (alpha 1 PI) partially blocks the effect. Charge interactions also appear to be important because the polyanions heparin and sulfated dextran completely blocked increased permeability following elastase but only partially blocked elastolytic activity in isotonic solutions.(ABSTRACT TRUNCATED AT 250 WORDS)
journal_name
Am J Respir Cell Mol Biolauthors
Peterson MW,Walter ME,Nygaard SDdoi
10.1165/ajrcmb.13.6.7576710subject
Has Abstractpub_date
1995-12-01 00:00:00pages
719-27issue
6eissn
1044-1549issn
1535-4989journal_volume
13pub_type
杂志文章abstract::Chloride (Cl(-)) movement across fetal lung epithelia is thought to be mediated by the sodium-potassium-2-Cl(-) cotransporter NKCC1. We studied the role of NKCC1 in Cl(-) and liquid secretion in late-gestation NKCC-null (-/-) and littermate control fetal mouse lung. NKCC -/- mice had decreased lung water compared with...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
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journal_title:American journal of respiratory cell and molecular biology
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journal_title:American journal of respiratory cell and molecular biology
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journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
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journal_title:American journal of respiratory cell and molecular biology
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journal_title:American journal of respiratory cell and molecular biology
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journal_title:American journal of respiratory cell and molecular biology
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doi:10.1165/ajrcmb.20.2.3148
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journal_title:American journal of respiratory cell and molecular biology
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更新日期:2012-10-01 00:00:00
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journal_title:American journal of respiratory cell and molecular biology
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更新日期:2002-04-01 00:00:00
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journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2008-0417OC
更新日期:2009-11-01 00:00:00
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journal_title:American journal of respiratory cell and molecular biology
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journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
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更新日期:1989-12-01 00:00:00
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journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2007-0010OC
更新日期:2008-01-01 00:00:00
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doi:10.1165/rcmb.2014-0334OC
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journal_title:American journal of respiratory cell and molecular biology
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journal_title:American journal of respiratory cell and molecular biology
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journal_title:American journal of respiratory cell and molecular biology
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journal_title:American journal of respiratory cell and molecular biology
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journal_title:American journal of respiratory cell and molecular biology
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journal_title:American journal of respiratory cell and molecular biology
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journal_title:American journal of respiratory cell and molecular biology
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journal_title:American journal of respiratory cell and molecular biology
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journal_title:American journal of respiratory cell and molecular biology
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abstract::We examined the mechanisms underlying tachyphylaxis to beta-adrenergic receptor agonists (beta-agonists) in tracheal smooth muscle. Simultaneous measurements of isometric tension and intracellular Ca2+ concentration ([Ca2+]i) using fura-2-loaded guinea pig tracheas showed that the inhibitory effects of isoproterenol (...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
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更新日期:2003-09-01 00:00:00
abstract::The asthmatic lung is prone to respiratory viral infections that exacerbate the symptoms of the underlying disease. Recent work has suggested that a deficient T-helper cell type 1 response in early life may lead to these aberrant antiviral responses. To study the development of long-term dysregulation of innate respon...
journal_title:American journal of respiratory cell and molecular biology
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