AJP - Lung AJP: Regulatory, Integrative and Comparative Physiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Lung Cell Mol Physiol 278: L193-L201, 2000;
1040-0605/00 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (134)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Akers, I. A.
Right arrow Articles by McAnulty, R. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Akers, I. A.
Right arrow Articles by McAnulty, R. J.
Vol. 278, Issue 1, L193-L201, January 2000

Mast cell tryptase stimulates human lung fibroblast proliferation via protease-activated receptor-2

Ian A. Akers1, Maddy Parsons1, Michael R. Hill1, Morley D. Hollenberg2, Shahin Sanjar3, Geoffrey J. Laurent1, and Robin J. McAnulty1

1 Centre for Cardiopulmonary Biochemistry and Respiratory Medicine, The Royal Free and University College Medical School, The Rayne Institute, London WC1E 6JJ; 3 Respiratory Diseases Unit, Glaxo Wellcome Research and Development Limited, Medicines Research Centre, Stevenage SG1 2NY, United Kingdom; and 2 Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada T2N 4N1

Mast cells play a potentially important role in fibroproliferative diseases, releasing mediators including tryptase that are capable of stimulating fibroblast proliferation and procollagen synthesis. The mechanism by which tryptase stimulates fibroblast proliferation is unclear, although recent studies suggest it can activate protease-activated receptor (PAR)-2. We therefore investigated the role of PAR-2 in tryptase-induced proliferation of human fetal lung and adult lung parenchymal and airway fibroblasts and, for comparative purposes, adult dermal fibroblasts. Tryptase (0.7-70 mU/ml) induced concentration-dependent increases in proliferation of all fibroblasts studied. Antipain, bis(5-amidino-2-benzimidazolyl)methane, and benzamidine inhibited tryptase-induced fibroblast proliferation, demonstrating that proteolytic activity is required for the proliferative effects of tryptase. RT-PCR demonstrated the presence of PAR-2 mRNA, and immunohistochemical staining localized PAR-2 to the cell surface of lung fibroblasts. In addition, specific PAR-2 activating peptides, SLIGKV and SLIGRL, mimicked the proliferative effects of tryptase. In contrast, human dermal fibroblasts only weakly stained with the PAR-2 antibody, PAR-2 mRNA was almost undetectable, and fibroblasts did not respond to PAR-2 activating peptides. These results suggest that tryptase induces lung, but not dermal, fibroblast proliferation via activation of PAR-2 and are consistent with the hypothesis that the release of tryptase from activated mast cells may play an important role in the fibroproliferative response observed in asthma, chronic obstructive pulmonary disease, and patients with pulmonary fibrosis.

asthma; airway remodeling; interstitial fibrosis; serine proteinase


This article has been cited by other articles:


Home page
 Exp PhysiolHome page
Q. Gu and L.-Y. Lee
Effect of protease-activated receptor 2 activation on single TRPV1 channel activities in rat vagal pulmonary sensory neurons
Exp Physiol, August 1, 2009; 94(8): 928 - 936.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
A. Margulis, K. H. Nocka, N. L. Wood, S. F. Wolf, S. J. Goldman, and M. T. Kasaian
MMP dependence of fibroblast contraction and collagen production induced by human mast cell activation in a three-dimensional collagen lattice
Am J Physiol Lung Cell Mol Physiol, February 1, 2009; 296(2): L236 - L247.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
V. Shpacovitch, M. Feld, M. D. Hollenberg, T. A. Luger, and M. Steinhoff
Role of protease-activated receptors in inflammatory responses, innate and adaptive immunity
J. Leukoc. Biol., June 1, 2008; 83(6): 1309 - 1322.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
C. S. Mullan, M. Riley, D. Clarke, A. Tatler, A. Sutcliffe, A. J. Knox, and L. Pang
{beta}-Tryptase Regulates IL-8 Expression in Airway Smooth Muscle Cells by a PAR-2-Independent Mechanism
Am. J. Respir. Cell Mol. Biol., May 1, 2008; 38(5): 600 - 608.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
R. Ramachandran, L. R. Sadofsky, Y. Xiao, A. Botham, M. Cowen, A. H. Morice, and S. J Compton
Inflammatory mediators modulate thrombin and cathepsin-G signaling in human bronchial fibroblasts by inducing expression of proteinase-activated receptor-4
Am J Physiol Lung Cell Mol Physiol, March 1, 2007; 292(3): L788 - L798.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
Q. Gu and L.-Y. Lee
Hypersensitivity of pulmonary chemosensitive neurons induced by activation of protease-activated receptor-2 in rats
J. Physiol., August 1, 2006; 574(3): 867 - 876.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
R. Ramachandran, A. H. Morice, and S. J. Compton
Proteinase-Activated Receptor2 Agonists Upregulate Granulocyte Colony-Stimulating Factor, IL-8, and VCAM-1 Expression in Human Bronchial Fibroblasts
Am. J. Respir. Cell Mol. Biol., July 1, 2006; 35(1): 133 - 141.
[Abstract] [Full Text] [PDF]

Home page
 Ann Rheum DisHome page
S R Atkins, E L Matteson, J L Myers, J H Ryu, and T Bongartz
Morphological and quantitative assessment of mast cells in rheumatoid arthritis associated non-specific interstitial pneumonia and usual interstitial pneumonia.
Ann Rheum Dis, May 1, 2006; 65(5): 677 - 680.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
J. K. Brown, M. D. Hollenberg, and C. A. Jones
Tryptase activates phosphatidylinositol 3-kinases proteolytically independently from proteinase-activated receptor-2 in cultured dog airway smooth muscle cells
Am J Physiol Lung Cell Mol Physiol, February 1, 2006; 290(2): L259 - L269.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
R. Matsushima, A. Takahashi, Y. Nakaya, H. Maezawa, M. Miki, Y. Nakamura, F. Ohgushi, and S. Yasuoka
Human airway trypsin-like protease stimulates human bronchial fibroblast proliferation in a protease-activated receptor-2-dependent pathway
Am J Physiol Lung Cell Mol Physiol, February 1, 2006; 290(2): L385 - L395.
[Abstract] [Full Text] [PDF]

Home page
 GutHome page
S Al-Haddad and R H Riddell
The role of eosinophils in inflammatory bowel disease
Gut, December 1, 2005; 54(12): 1674 - 1675.
[Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
E. Sokolova, Z. Grishina, F. Buhling, T. Welte, and G. Reiser
Protease-activated receptor-1 in human lung fibroblasts mediates a negative feedback downregulation via prostaglandin E2
Am J Physiol Lung Cell Mol Physiol, May 1, 2005; 288(5): L793 - L802.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M. Boerma, J. Wang, J. Wondergem, J. Joseph, X. Qiu, R. H. Kennedy, and M. Hauer-Jensen
Influence of Mast Cells on Structural and Functional Manifestations of Radiation-Induced Heart Disease
Cancer Res., April 15, 2005; 65(8): 3100 - 3107.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
A. Masamune, K. Kikuta, M. Satoh, N. Suzuki, and T. Shimosegawa
Protease-Activated Receptor-2-Mediated Proliferation and Collagen Production of Rat Pancreatic Stellate Cells
J. Pharmacol. Exp. Ther., February 1, 2005; 312(2): 651 - 658.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
V. S. OSSOVSKAYA and N. W. BUNNETT
Protease-Activated Receptors: Contribution to Physiology and Disease
Physiol Rev, April 1, 2004; 84(2): 579 - 621.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
S. M. Fitzgerald, S. A. Lee, H. K. Hall, D. S. Chi, and G. Krishnaswamy
Human Lung Fibroblasts Express Interleukin-6 in Response to Signaling after Mast Cell Contact
Am. J. Respir. Cell Mol. Biol., April 1, 2004; 30(4): 585 - 593.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
R. S. Lan, G. A. Stewart, R. G. Goldie, and P. J. Henry
Altered expression and in vivo lung function of protease-activated receptors during influenza A virus infection in mice
Am J Physiol Lung Cell Mol Physiol, February 1, 2004; 286(2): L388 - L398.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
G. Grandaliano, P. Pontrelli, G. Cerullo, R. Monno, E. Ranieri, M. Ursi, A. Loverre, L. Gesualdo, and F. P. Schena
Protease-Activated Receptor-2 Expression in IgA Nephropathy: A Potential Role in the Pathogenesis of Interstitial Fibrosis
J. Am. Soc. Nephrol., August 1, 2003; 14(8): 2072 - 2083.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S. H. Cho, Z. Yao, S.-W. Wang, R. F. Alban, R. G. Barbers, S. W. French, and C. K. Oh
Regulation of Activin A Expression in Mast Cells and Asthma: Its Effect on the Proliferation of Human Airway Smooth Muscle Cells
J. Immunol., April 15, 2003; 170(8): 4045 - 4052.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
R. Lang, P. I. Song, F. J. Legat, R. M. Lavker, B. Harten, H. Kalden, E. F. Grady, N. W. Bunnett, C. A. Armstrong, and J. C. Ansel
Human Corneal Epithelial Cells Express Functional PAR-1 and PAR-2
Invest. Ophthalmol. Vis. Sci., January 1, 2003; 44(1): 99 - 105.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
F. Schmidlin, S. Amadesi, K. Dabbagh, D. E. Lewis, P. Knott, N. W. Bunnett, P. R. Gater, P. Geppetti, C. Bertrand, and M. E. Stevens
Protease-Activated Receptor 2 Mediates Eosinophil Infiltration and Hyperreactivity in Allergic Inflammation of the Airway
J. Immunol., November 1, 2002; 169(9): 5315 - 5321.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
V. Temkin, B. Kantor, V. Weg, M.-L. Hartman, and F. Levi-Schaffer
Tryptase Activates the Mitogen-Activated Protein Kinase/Activator Protein-1 Pathway in Human Peripheral Blood Eosinophils, Causing Cytokine Production and Release
J. Immunol., September 1, 2002; 169(5): 2662 - 2669.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
W. M. Abraham
Tryptase: potential role in airway inflammation and remodeling
Am J Physiol Lung Cell Mol Physiol, February 1, 2002; 282(2): L193 - L196.
[Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
J. K. Brown, C. A. Jones, L. A. Rooney, G. H. Caughey, and I. P. Hall
Tryptase's potent mitogenic effects in human airway smooth muscle cells are via nonproteolytic actions
Am J Physiol Lung Cell Mol Physiol, February 1, 2002; 282(2): L197 - L206.
[Abstract] [Full Text] [PDF]

Home page
 ThoraxHome page
D Miotto, M D Hollenberg, N W Bunnett, A Papi, F Braccioni, P Boschetto, F Rea, A Zuin, P Geppetti, M Saetta, et al.
Expression of protease activated receptor-2 (PAR-2) in central airways of smokers and non-smokers
Thorax, February 1, 2002; 57(2): 146 - 151.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
L. S. Chambers, J. L. Black, P. Poronnik, and P. R. A. Johnson
Functional effects of protease-activated receptor-2 stimulation on human airway smooth muscle
Am J Physiol Lung Cell Mol Physiol, December 1, 2001; 281(6): L1369 - L1378.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
C. P. SOMMERHOFF
Mast Cell Tryptases and Airway Remodeling
Am. J. Respir. Crit. Care Med., November 15, 2001; 164(10): S52 - 58.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
F. SCHMIDLIN, S. AMADESI, R. VIDIL, M. TREVISANI, N. MARTINET, G. CAUGHEY, M. TOGNETTO, G. CAVALLESCO, C. MAPP, P. GEPPETTI, et al.
Expression and Function of Proteinase-activated Receptor 2 in Human Bronchial Smooth Muscle
Am. J. Respir. Crit. Care Med., October 1, 2001; 164(7): 1276 - 1281.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
S. KONDO, S. KAGAMI, H. KIDO, F. STRUTZ, G. A. MULLER, and Y. KURODA
Role of Mast Cell Tryptase in Renal Interstitial Fibrosis
J. Am. Soc. Nephrol., August 1, 2001; 12(8): 1668 - 1676.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
M. Oido-Mori, R. Rezzonico, P.-L. Wang, Y. Kowashi, J.-M. Dayer, P. C. Baehni, and C. Chizzolini
Porphyromonas gingivalis Gingipain-R Enhances Interleukin-8 but Decreases Gamma Interferon-Inducible Protein 10 Production by Human Gingival Fibroblasts in Response to T-Cell Contact
Infect. Immun., July 1, 2001; 69(7): 4493 - 4501.
[Abstract] [Full Text] [PDF]

Home page
 Pharmacol. Rev.Home page
S. R. Macfarlane, M. J. Seatter, T. Kanke, G. D. Hunter, and R. Plevin
Proteinase-Activated Receptors
Pharmacol. Rev., June 1, 2001; 53(2): 245 - 282.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
M. R. D'Andrea, C. K. Derian, R. J. Santulli, and P. Andrade-Gordon
Differential Expression of Protease-Activated Receptors-1 and -2 in Stromal Fibroblasts of Normal, Benign, and Malignant Human Tissues
Am. J. Pathol., June 1, 2001; 158(6): 2031 - 2041.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
J. K. Brown, C. A. Jones, L. A. Rooney, and G. H. Caughey
Mast Cell Tryptase Activates Extracellular-Regulated Kinases (p44/p42) in Airway Smooth-Muscle Cells . Importance of Proteolytic Events, Time Course, and Role in Mediating Mitogenesis
Am. J. Respir. Cell Mol. Biol., February 1, 2001; 24(2): 146 - 154.
[Abstract] [Full Text]

Home page
 BloodHome page
H. Tapper and H. Herwald
Modulation of hemostatic mechanisms in bacterial infectious diseases
Blood, October 1, 2000; 96(7): 2329 - 2337.
[Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
R. C. Chambers, P. Leoni, O. P. Blanc-Brude, D. E. Wembridge, and G. J. Laurent
Thrombin Is a Potent Inducer of Connective Tissue Growth Factor Production via Proteolytic Activation of Protease-activated Receptor-1
J. Biol. Chem., November 3, 2000; 275(45): 35584 - 35591.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
J. J. Ubl, Z. V. Grishina, T. K. Sukhomlin, T. Welte, F. Sedehizade, and G. Reiser
Human bronchial epithelial cells express PAR-2 with different sensitivity to thermolysin
Am J Physiol Lung Cell Mol Physiol, June 1, 2002; 282(6): L1339 - L1348.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online