Abstract:
:In addition to its central role in hemostasis, thrombin may play a role in inflammation and remodeling. To investigate the contribution of thrombin to allergic airway inflammation in asthma, we used an enzymatic assay to determine thrombin activity in bronchoalveolar lavage fluid obtained from 19 subjects with atopic asthma before (Day 0) and 48 hours after (Day 2) segmental bronchoprovocation with antigen. Thrombin activity increased from 0 (0, 2.9) on Day 1 to 41.1 (0.3, 75.6) U x 10(-3)/ml on Day 2 (p = 0.002) and correlated with total protein levels in lavage fluid on Day 2 (r = 0.885, p < 0.001). After antigen challenge, thrombin activity also showed significant correlations with interleukin-5 (r = 0.66, p = 0.002), transforming growth factor beta1 (r = 0.70, p < 0.001), fibronectin (r = 0.85, p < 0.001) and tissue factor (r = 0.55, p = 0.03) levels in lavage fluid. Furthermore, Day 2, but not Day 0 lavage fluid, induced proliferation of human airway fibroblasts. This mitogenic effect was significantly reduced with hirudin, a specific thrombin inhibitor. Taken together, our findings suggest that allergen-driven airway inflammation in asthma is associated with enhanced potential for fibroblast proliferation that is related, at least in part, to increased thrombin activity. We propose that enhanced thrombin activity provides a potential link between allergic inflammation and initiation of airway remodeling.
journal_name
Am J Respir Crit Care Medauthors
Terada M,Kelly EA,Jarjour NNdoi
10.1164/rccm.200308-1156OCkeywords:
subject
Has Abstractpub_date
2004-02-01 00:00:00pages
373-7issue
3eissn
1073-449Xissn
1535-4970pii
200308-1156OCjournal_volume
169pub_type
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journal_title:American journal of respiratory and critical care medicine
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journal_title:American journal of respiratory and critical care medicine
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pub_type: 杂志文章
doi:10.1164/ajrccm.152.4.7551390
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abstract:RATIONALE:Exercise-induced bronchoconstriction (EIB) is a highly prevalent condition with unclear pathogenesis. Two competing theories of the pathogenesis of EIB differ regarding the inflammatory basis of this condition. OBJECTIVES:Our goals were to establish whether epithelial cell and mast cell activation with relea...
journal_title:American journal of respiratory and critical care medicine
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journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2000-07-01 00:00:00
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更新日期:2016-08-15 00:00:00
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pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2002-08-01 00:00:00
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journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.164.4.2005127
更新日期:2001-08-15 00:00:00
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更新日期:1998-05-01 00:00:00
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journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1995-10-01 00:00:00
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更新日期:2001-03-01 00:00:00
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journal_title:American journal of respiratory and critical care medicine
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更新日期:1994-07-01 00:00:00
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更新日期:2013-12-15 00:00:00
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更新日期:1999-11-01 00:00:00
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更新日期:2011-11-15 00:00:00
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journal_title:American journal of respiratory and critical care medicine
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更新日期:2007-11-01 00:00:00
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更新日期:2004-04-01 00:00:00
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journal_title:American journal of respiratory and critical care medicine
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更新日期:2003-01-01 00:00:00