Published ahead of print on November 20, 2003, doi:10.1164/rccm.200308-1156OC
American Journal of Respiratory and Critical Care Medicine Vol 169. pp. 373-377, (2004)
© 2004 American Thoracic Society
Increased Thrombin Activity after Allergen Challenge
A Potential Link to Airway Remodeling?
Masaki Terada,
Elizabeth A. B. Kelly and
Nizar N. Jarjour
Pulmonary and Critical Care Medicine Section, Department of Medicine, University of Wisconsin, Madison, Wisconsin
Correspondence and requests for reprints should be addressed to Nizar N. Jarjour, M.D., Pulmonary and Critical Care Medicine Section, 600 Highland Avenue, CSC K4/930 (9988), University of Wisconsin School of Medicine, Madison, WI 53792. E-mail: nnj{at}medicine.wisc.edu
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 ß1 (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.
Key Words: asthma • bronchoalveolar lavage fluid • thrombin • fibroblasts
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