help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Published ahead of print on March 27, 2003, doi:10.1165/rcmb.2003-0034OC

Am. J. Respir. Cell Mol. Biol., Volume 29, Number 3, September 2003, 283-294

A more recent version of this article appeared on September 1, 2003
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
2003-0034OCv1
29/3/283    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 Owen, C. A
Right arrow Articles by Shapiro, S. D
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Owen, C. A
Right arrow Articles by Shapiro, S. D

Submitted on February 3, 2003
Revised on March 20, 2003

Inducible expression of TIMP-resistant matrix metalloproteinase-9 on the cell surface of neutrophils

Caroline A Owen1*, Zhuma Hu2, Brooke Barrick2, and Steven D Shapiro1

1 Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA, 2 Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, UT, USA

* To whom correspondence should be addressed. E-mail: cowen{at}rics.bwh.harvard.edu.

MMP-9 secreted by activated PMN may play roles in mediating lung injury by degrading extracellular matrix proteins. However, the mechanisms by which MMP-9 retains activity in the presence of TIMPs are not known. We show that MMP-9 is also expressed on the cell surface of PMN, and pro-inflammatory mediators induce up to 10-fold increases in cell surface expression of MMP-9. Stimulated human PMN express active forms of cell surface MMP which cleave the MMP substrate, McaPLGLDpaAR. Loss-of-function studies employing PMN from mice genetically deficient in MMP-9 (MMP-9-/-) demonstrate that membrane-bound MMP-9 contributes substantially to MMP-mediated surface-bound cleavage of McaPLGLDpaAR (~50%)and gelatin (~70%) by stimulated PMN. Like soluble MMP-9, membrane-bound MMP-9 cleaves McaPLGLDpaAR (kcat/kM = 82,000 M-1s-1), gelatin, type IV collagen, elastin and {alpha}1-proteinase inhibitor. However, in contrast to soluble MMP-9, membrane-bound MMP-9 is substantially resistant to inhibition by TIMPs. The IC50 for inhibition of membrane-bound MMP-9 by TIMP-1 and TIMP-2 are ~21-fold and ~68-fold higher, respectively, than those for inhibition of soluble MMP-9. The binding of MMP-9 to the plasma membrane of PMN enables it to evade inhibition by TIMPs, and thereby may alter the pericellular proteolytic balance in favor of extracellular matrix degradation. Membrane-bound MMP-9 on PMN may play pathogenetic roles in inflammatory lung diseases.




This article has been cited by other articles:


Home page
 Am. J. Respir. Cell Mol. Bio.Home page
R. Takamiya, C.-C. Hung, S. R. Hall, K. Fukunaga, T. Nagaishi, T. Maeno, C. Owen, A. A. Macias, L. E. Fredenburgh, A. Ishizaka, et al.
High-Mobility Group Box 1 Contributes to Lethality of Endotoxemia in Heme Oxygenase-1-Deficient Mice
Am. J. Respir. Cell Mol. Biol., August 1, 2009; 41(2): 129 - 135.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. ProteomicsHome page
T. Vaisar, S. Y. Kassim, I. G. Gomez, P. S. Green, S. Hargarten, P. J. Gough, W. C. Parks, C. L. Wilson, E. W. Raines, and J. W. Heinecke
MMP-9 Sheds the {beta}2 Integrin Subunit (CD18) from Macrophages
Mol. Cell. Proteomics, May 1, 2009; 8(5): 1044 - 1060.
[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
E. Cuadrado, L. Ortega, M. Hernandez-Guillamon, A. Penalba, I. Fernandez-Cadenas, A. Rosell, and J. Montaner
Tissue plasminogen activator (t-PA) promotes neutrophil degranulation and MMP-9 release
J. Leukoc. Biol., July 1, 2008; 84(1): 207 - 214.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
M. Lin, P. Jackson, A. M. Tester, E. Diaconu, C. M. Overall, J. E. Blalock, and E. Pearlman
Matrix Metalloproteinase-8 Facilitates Neutrophil Migration through the Corneal Stromal Matrix by Collagen Degradation and Production of the Chemotactic Peptide Pro-Gly-Pro
Am. J. Pathol., July 1, 2008; 173(1): 144 - 153.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
G. M. Albaiceta, A. Gutierrez-Fernandez, D. Parra, A. Astudillo, E. Garcia-Prieto, F. Taboada, and A. Fueyo
Lack of matrix metalloproteinase-9 worsens ventilator-induced lung injury
Am J Physiol Lung Cell Mol Physiol, March 1, 2008; 294(3): L535 - L543.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
K. J. Greenlee, Z. Werb, and F. Kheradmand
Matrix Metalloproteinases in Lung: Multiple, Multifarious, and Multifaceted
Physiol Rev, January 1, 2007; 87(1): 69 - 98.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
E. K. Chu, J. Cheng, J. S. Foley, B. H. Mecham, C. A. Owen, K. J. Haley, T. J. Mariani, I. S. Kohane, D. J. Tschumperlin, and J. M. Drazen
Induction of the Plasminogen Activator System by Mechanical Stimulation of Human Bronchial Epithelial Cells
Am. J. Respir. Cell Mol. Biol., December 1, 2006; 35(6): 628 - 638.
[Abstract] [Full Text] [PDF]

Home page
 Int ImmunolHome page
M. Suzukawa, A. Komiya, M. Iikura, H. Nagase, C. Yoshimura-Uchiyama, H. Yamada, H. Kawasaki, K. Ohta, K. Matsushima, K. Hirai, et al.
Trans-basement membrane migration of human basophils: role of matrix metalloproteinase-9
Int. Immunol., November 1, 2006; 18(11): 1575 - 1583.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
A. Zijlstra, M. Seandel, T. A. Kupriyanova, J. J. Partridge, M. A. Madsen, E. A. Hahn-Dantona, J. P. Quigley, and E. I. Deryugina
Proangiogenic role of neutrophil-like inflammatory heterophils during neovascularization induced by growth factors and human tumor cells
Blood, January 1, 2006; 107(1): 317 - 327.
[Abstract] [Full Text] [PDF]

Home page
 SURG INNOVHome page
A. Belizon, I. Kirman, M. Karten, S. Jain, and R. L. Whelan
Rapid Increase in Serum Levels of Matrix Metalloproteinase-9 (MMP-9) Postoperatively is Associated With a Decrease in the Amount of Intracellular MMP-9
Surgical Innovation, December 1, 2005; 12(4): 333 - 337.
[Abstract] [PDF]

Home page
 Proc Am Thorac SocHome page
C. A. Owen
Proteinases and Oxidants as Targets in the Treatment of Chronic Obstructive Pulmonary Disease
Proceedings of the ATS, November 1, 2005; 2(4): 373 - 385.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
J. M. Gidday, Y. G. Gasche, J.-C. Copin, A. R. Shah, R. S. Perez, S. D. Shapiro, P. H. Chan, and T. S. Park
Leukocyte-derived matrix metalloproteinase-9 mediates blood-brain barrier breakdown and is proinflammatory after transient focal cerebral ischemia
Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H558 - H568.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
E. Daimon and Y. Wada
Role of Neutrophils in Matrix Metalloproteinase Activity in the Preimplantation Mouse Uterus
Biol Reprod, July 1, 2005; 73(1): 163 - 171.
[Abstract] [Full Text] [PDF]

Home page
 Pharmacol. Rev.Home page
P. J. Barnes
Mediators of Chronic Obstructive Pulmonary Disease
Pharmacol. Rev., December 1, 2004; 56(4): 515 - 548.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
P. Baluk, W. W. Raymond, E. Ator, L. M. Coussens, D. M. McDonald, and G. H. Caughey
Matrix metalloproteinase-2 and -9 expression increases in Mycoplasma-infected airways but is not required for microvascular remodeling
Am J Physiol Lung Cell Mol Physiol, August 1, 2004; 287(2): L307 - L317.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
J.-P. Levesque, F. Liu, P. J. Simmons, T. Betsuyaku, R. M. Senior, C. Pham, and D. C. Link
Characterization of hematopoietic progenitor mobilization in protease-deficient mice
Blood, July 1, 2004; 104(1): 65 - 72.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
C. A. Owen, Z. Hu, C. Lopez-Otin, and S. D. Shapiro
Membrane-Bound Matrix Metalloproteinase-8 on Activated Polymorphonuclear Cells Is a Potent, Tissue Inhibitor of Metalloproteinase-Resistant Collagenase and Serpinase
J. Immunol., June 15, 2004; 172(12): 7791 - 7803.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. Stefanidakis, T. Ruohtula, N. Borregaard, C. G. Gahmberg, and E. Koivunen
Intracellular and Cell Surface Localization of a Complex between {alpha}M{beta}2 Integrin and Promatrix Metalloproteinase-9 Progelatinase in Neutrophils
J. Immunol., June 1, 2004; 172(11): 7060 - 7068.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 2003 American Thoracic Society. 		  CCM abstracts