Published ahead of print on November 20, 2003, doi:10.1164/rccm.200308-1156OC
Am. J. Respir. Crit. Care Med., Volume 169, Number 3, February 2004, 373-377
A more recent version of this article appeared on February 1, 2004
Submitted on August 20, 2003
Accepted on November 18, 2003
Increased thrombin activity following allergen challenge: a potential link to airway remodeling?
Masaki Terada1, Elizabeth A.B. Kelly1, and Nizar N Jarjour1*
1 Medicine, Pulmonary and Critical Care Section, University of Wisconsin, Madison, WI, USA
* To whom correspondence should be addressed. 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 atopic asthma subjects before (Day 0) and 48 hours after (Day 2) segmental bronchoprovocation with antigen. Thrombin activity increased from 0 (0, 2.9) to 41.1 (0.3, 75.6) units 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-beta 1 (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
This article has been cited by other articles:
|
|
|
|
 
E. Ostrowska, E. Sokolova, and G. Reiser
PAR-2 activation and LPS synergistically enhance inflammatory signaling in airway epithelial cells by raising PAR expression level and interleukin-8 release
Am J Physiol Lung Cell Mol Physiol,
November 1, 2007;
293(5):
L1208 - L1218.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Kanazawa and T. Yoshikawa
Up-Regulation of Thrombin Activity Induced by Vascular Endothelial Growth Factor in Asthmatic Airways
Chest,
October 1, 2007;
132(4):
1169 - 1174.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. M. Kassel, N. A. Schulte, S. M. Parker, A. D. Lanik, and M. L. Toews
Lysophosphatidic Acid Decreases Epidermal Growth Factor Receptor Binding in Airway Epithelial Cells
J. Pharmacol. Exp. Ther.,
October 1, 2007;
323(1):
109 - 118.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. A. Paveglio, J. Allard, J. Mayette, L. A. Whittaker, I. Juncadella, J. Anguita, and M. E. Poynter
The Tick Salivary Protein, Salp15, Inhibits the Development of Experimental Asthma
J. Immunol.,
June 1, 2007;
178(11):
7064 - 7071.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Henderson, L. J. Markwick, S. R. Elshaw, A. M. Freyer, A. J. Knox, and S. R. Johnson
Collagen I and thrombin activate MMP-2 by MMP-14-dependent and -independent pathways: implications for airway smooth muscle migration
Am J Physiol Lung Cell Mol Physiol,
April 1, 2007;
292(4):
L1030 - L1038.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Shinagawa, J. A. Martin, V. A. Ploplis, and F. J. Castellino
Coagulation Factor Xa Modulates Airway Remodeling in a Murine Model of Asthma
Am. J. Respir. Crit. Care Med.,
January 15, 2007;
175(2):
136 - 143.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Q. Fang, X. Liu, M. Al-Mugotir, T. Kobayashi, S. Abe, T. Kohyama, and S. I. Rennard
Thrombin and TNF-{alpha}/IL-1beta Synergistically Induce Fibroblast-Mediated Collagen Gel Degradation
Am. J. Respir. Cell Mol. Biol.,
December 1, 2006;
35(6):
714 - 721.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C.-H. Lin, H.-W. Cheng, M.-J. Hsu, M.-C. Chen, C.-C. Lin, and B.-C. Chen
c-Src Mediates Thrombin-Induced NF-{kappa}B Activation and IL-8/CXCL8 Expression in Lung Epithelial Cells.
J. Immunol.,
September 1, 2006;
177(5):
3427 - 3438.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Gavara, R. Sunyer, P. Roca-Cusachs, R. Farre, M. Rotger, and D. Navajas
Thrombin-induced contraction in alveolar epithelial cells probed by traction microscopy
J Appl Physiol,
August 1, 2006;
101(2):
512 - 520.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. J. Laurent
No Bit PARt for PAR-1
Am. J. Respir. Cell Mol. Biol.,
September 1, 2005;
33(3):
213 - 215.
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. A. Weiss, L. A. Lester, J. E. Gern, R. L. Wolf, R. Parry, R. F. Lemanske, J. Solway, and C. Ober
Variation in ITGB3 Is Associated with Asthma and Sensitization to Mold Allergen in Four Populations
Am. J. Respir. Crit. Care Med.,
July 1, 2005;
172(1):
67 - 73.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Fabbri, S. P. Peters, I. Pavord, S. E. Wenzel, S. C. Lazarus, W. MacNee, F. Lemaire, and E. Abraham
Allergic Rhinitis, Asthma, Airway Biology, and Chronic Obstructive Pulmonary Disease in AJRCCM in 2004
Am. J. Respir. Crit. Care Med.,
April 1, 2005;
171(7):
686 - 698.
[Full Text]
[PDF]
|
|
|
Copyright © 2003 American Thoracic Society
|
|
|
