help button home button
AJRCCM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Published ahead of print on November 20, 2003, doi:10.1164/rccm.200308-1156OC
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Online Supplement
Right arrow All Versions of this Article:
200308-1156OCv1
169/3/373    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Terada, M.
Right arrow Articles by Jarjour, N. N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Terada, M.
Right arrow Articles by Jarjour, N. N.
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




This article has been cited by other articles:


Home page
 J. Immunol.Home page
C.-C. Yu, M.-J. Hsu, M.-L. Kuo, R. F.-C. Chen, M.-C. Chen, K.-J. Bai, M.-C. Yu, B.-C. Chen, and C.-H. Lin
Thrombin-Induced Connective Tissue Growth Factor Expression in Human Lung Fibroblasts Requires the ASK1/JNK/AP-1 Pathway
J. Immunol., June 15, 2009; 182(12): 7916 - 7927.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
K. Shinagawa, V. A. Ploplis, and F. J. Castellino
A severe deficiency of coagulation factor VIIa results in attenuation of the asthmatic response in mice
Am J Physiol Lung Cell Mol Physiol, May 1, 2009; 296(5): L763 - L770.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
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]

Home page
 ChestHome page
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]

Home page
 J. Pharmacol. Exp. Ther.Home page
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]

Home page
 J. Immunol.Home page
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]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
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]

Home page
 Am. J. Respir. Crit. Care Med.Home page
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]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
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]

Home page
 J. Immunol.Home page
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]

Home page
 J. Appl. Physiol.Home page
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]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
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]

Home page
 Am. J. Respir. Crit. Care Med.Home page
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]

Home page
 Am. J. Respir. Crit. Care Med.Home page
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]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Cell Mol. Biol.
Copyright © 2004 American Thoracic Society 		  SOTA, FL