| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Department of Pathology, University of Michigan, Ann Arbor, MI 48109; and
Pathology and Experimental Toxicology and Biotechnology Department, Parke-Davis Pharmaceutical Research, Warner-Lambert Co., Ann Arbor, MI 48105
Inflammatory lung injury is probably regulated by the balance
between proteases and protease inhibitors together with oxidants and
antioxidants, and proinflammatory and anti-inflammatory cytokines.
Rat tissue inhibitor of metalloprotease-2 (TIMP-2) and secreted
leukoprotease inhibitor (SLPI) were cloned, expressed, and shown to be
up-regulated at the levels of mRNA and protein during lung inflammation
in rats induced by deposition of IgG immune complexes. Using
immunoaffinity techniques, endogenous TIMP-2 in the inflamed lung was
shown to exist as a complex with 72- and 92-kDa metalloproteinases
(MMP-2 and MMP-9). In inflamed lung both TIMP-2 and SLPI appeared to
exist as enzyme inhibitor complexes. Lung expression of both TIMP-2 and
SLPI appeared to involve endothelial and epithelial cells as well as
macrophages. To assess how these endogenous inhibitors might affect the
lung inflammatory response, animals were treated with polyclonal rabbit
Abs to rat TIMP-2 or SLPI. This intervention resulted in significant
intensification of lung injury (as revealed by extravascular leak of
albumin) and substantially increased neutrophil accumulation, as
determined by cell content in bronchoalveolar lavage (BAL) fluids.
These events were correlated with increased levels of C5a-related
chemotactic activity in BAL fluids, while BAL levels of TNF-
and
chemokines were not affected by treatment with anti-TIMP-2 or
anti-SLPI. The data suggest that endogenous TIMP-2 and SLPI
dynamically regulate the intensity of lung inflammatory injury, doing
so at least in part by affecting the generation of the inflammatory
mediator, C5a.
This article has been cited by other articles:
|
|
 |
|
  M. Shyamsundar, S. T. W. McKeown, C. M. O'Kane, T. R. Craig, V. Brown, D. R. Thickett, M. A. Matthay, C. C. Taggart, J. T. Backman, J. S. Elborn, et al. Simvastatin Decreases Lipopolysaccharide-induced Pulmonary Inflammation in Healthy Volunteers Am. J. Respir. Crit. Care Med., June 15, 2009; 179(12): 1107 - 1114. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P T G Elkington and J S Friedland Matrix metalloproteinases in destructive pulmonary pathology Thorax, March 1, 2006; 61(3): 259 - 266. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.-H. Kim, K. Burkhart, P. Chen, C. W. Frevert, J. Randolph-Habecker, R. C. Hackman, P. D. Soloway, and D. K. Madtes Tissue Inhibitor of Metalloproteinase-1 Deficiency Amplifies Acute Lung Injury in Bleomycin-Exposed Mice Am. J. Respir. Cell Mol. Biol., September 1, 2005; 33(3): 271 - 279. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Doumas, A. Kolokotronis, and P. Stefanopoulos Anti-Inflammatory and Antimicrobial Roles of Secretory Leukocyte Protease Inhibitor Infect. Immun., March 1, 2005; 73(3): 1271 - 1274. [Full Text] [PDF]
|
|
|
|
|
|
C. M. Greene, N. G. McElvaney, S. J. O'Neill, and C. C. Taggart Secretory Leucoprotease Inhibitor Impairs Toll-Like Receptor 2- and 4-Mediated Responses in Monocytic Cells Infect. Immun., June 1, 2004; 72(6): 3684 - 3687. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. I. Ekekezie, D. W. Thibeault, S. D. Simon, M. Norberg, J. D. Merrill, R. A. Ballard, P. L. Ballard, and W. E. Truog Low Levels of Tissue Inhibitors of Metalloproteinases With a High Matrix Metalloproteinase-9/Tissue Inhibitor of Metalloproteinase-1 Ratio Are Present in Tracheal Aspirate Fluids of Infants Who Develop Chronic Lung Disease Pediatrics, June 1, 2004; 113(6): 1709 - 1714. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Wex, G. Treiber, M. Nilius, M. Vieth, A. Roessner, and P. Malfertheiner Helicobacter pylori-Mediated Gastritis Induces Local Downregulation of Secretory Leukocyte Protease Inhibitor in the Antrum Infect. Immun., April 1, 2004; 72(4): 2383 - 2385. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Wang, X. Li, L. Xu, Y. Zhan, S. Yaish-Ohad, J. A. Erhardt, F. C. Barone, and G. Z. Feuerstein Up-Regulation of Secretory Leukocyte Protease Inhibitor (SLPI) in the Brain after Ischemic Stroke: Adenoviral Expression of SLPI Protects Brain from Ischemic Injury Mol. Pharmacol., October 1, 2003; 64(4): 833 - 840. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-M. Sallenave, G. A. Cunningham, R. M. James, G. McLachlan, and C. Haslett Regulation of Pulmonary and Systemic Bacterial Lipopolysaccharide Responses in Transgenic Mice Expressing Human Elafin Infect. Immun., July 1, 2003; 71(7): 3766 - 3774. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Devoogdt, G. Hassanzadeh Ghassabeh, J. Zhang, L. Brys, P. De Baetselier, and H. Revets Secretory leukocyte protease inhibitor promotes the tumorigenic and metastatic potential of cancer cells PNAS, May 13, 2003; 100(10): 5778 - 5782. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Eichler, J F M. Bechtel, J. Schumacher, J. A Wermelt, K.-F. Klotz, and C. Bartels A rise of MMP-2 and MMP-9 in bronchoalveolar lavage fluid is associated with acute lung injury after cardiopulmonary bypass in a swine model Perfusion, March 1, 2003; 18(2): 107 - 113. [Abstract] [PDF]
|
|
|
|
 |
|
 V. D. Raykova, M. Glibetic, J. P. Ofenstein, and J. V. Aranda Nitric Oxide-Dependent Regulation of Pro-inflammatory Cytokines in Group B Streptococcal Inflammation of Rat Lung Ann. Clin. Lab. Sci., January 1, 2003; 33(1): 62 - 67. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Huber-Lang, E. M. Younkin, J. V. Sarma, N. Riedemann, S. R. McGuire, K. T. Lu, R. Kunkel, J. G. Younger, F. S. Zetoune, and P. A. Ward Generation of C5a by Phagocytic Cells Am. J. Pathol., November 1, 2002; 161(5): 1849 - 1859. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Zhang, R. C. M. Simmen, F. J. Michel, G. Zhao, D. Vale-Cruz, and F. A. Simmen Secretory Leukocyte Protease Inhibitor Mediates Proliferation of Human Endometrial Epithelial Cells by Positive and Negative Regulation of Growth-associated Genes J. Biol. Chem., August 9, 2002; 277(33): 29999 - 30009. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. I. de Boer Cytokines and Therapy in COPD* : A Promising Combination? Chest, May 1, 2002; 121(5_suppl): 209S - 218S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Cederqvist, T. Sorsa, T. Tervahartiala, P. Maisi, K. Reunanen, P. Lassus, and S. Andersson Matrix Metalloproteinases-2, -8, and -9 and TIMP-2 in Tracheal Aspirates From Preterm Infants With Respiratory Distress Pediatrics, September 1, 2001; 108(3): 686 - 692. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. B. Lentsch, A. Kato, J. T. Saari, and D. A. Schuschke Augmented metalloproteinase activity and acute lung injury in copper-deficient rats Am J Physiol Lung Cell Mol Physiol, August 1, 2001; 281(2): L387 - L393. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Simpson, W. A. H. Wallace, M. E. Marsden, J. R. W. Govan, D. J. Porteous, C. Haslett, and J.-M. Sallenave Adenoviral Augmentation of Elafin Protects the Lung Against Acute Injury Mediated by Activated Neutrophils and Bacterial Infection J. Immunol., August 1, 2001; 167(3): 1778 - 1786. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. Warner, C. S. Lewis, L. Beltran, E. M. Younkin, J. Varani, and K. J. Johnson The Role of Metalloelastase in Immune Complex-Induced Acute Lung Injury Am. J. Pathol., June 1, 2001; 158(6): 2139 - 2144. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. Warner, L. Beltran, E. M. Younkin, C. S. Lewis, S. J. Weiss, J. Varani, and K. J. Johnson Role of Stromelysin 1 and Gelatinase B in Experimental Acute Lung Injury Am. J. Respir. Cell Mol. Biol., May 1, 2001; 24(5): 537 - 544. [Abstract] [Full Text]
|
|
|
|
|
|
R.-F. Guo, A. B. Lentsch, R. L. Warner, M. Huber-Lang, J. V. Sarma, T. Hlaing, M. M. Shi, N. W. Lukacs, and P. A. Ward Regulatory Effects of Eotaxin on Acute Lung Inflammatory Injury J. Immunol., April 15, 2001; 166(8): 5208 - 5218. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.-Y. Su, R. H. Jaskot, J. Richards, S. R. Abramson, J. F. Woessner Jr., W.-H. Yu, and K. L. Dreher Induction of pulmonary matrilysin expression by combustion and ambient air particles Am J Physiol Lung Cell Mol Physiol, July 1, 2000; 279(1): L152 - L160. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Kernacki, R. Barrett, and L. D. Hazlett Evidence for TIMP-1 Protection Against P. aeruginosa-Induced Corneal Ulceration and Perforation Invest. Ophthalmol. Vis. Sci., December 1, 1999; 40(13): 3168 - 3176. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
