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Increased thrombin activity after allergen challenge: a potential link to airway remodeling?

Authors :
Terada M
Kelly EAB
Jarjour NN
Source :
American Journal of Respiratory & Critical Care Medicine; 2004, Vol. 169 Issue 3, p373-377, 5p
Publication Year :
2004

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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
1073449X
Volume :
169
Issue :
3
Database :
Complementary Index
Journal :
American Journal of Respiratory & Critical Care Medicine
Publication Type :
Academic Journal
Accession number :
106576005
Full Text :
https://doi.org/10.1164/rccm.200308-1156oc