Journal of the American Society of Nephrology
2007 JASN IMPACT FACTOR 7.111 HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP 
    advanced
CURRENT ISSUE ARCHIVES JASN Express ONLINE SUBMISSION


Published ahead of print on November 16, 2005
J Am Soc Nephrol 17: 131-140, 2006
© 2006 American Society of Nephrology
doi: 10.1681/ASN.2005010089
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
ASN.2005010089v1
17/1/131    most recent
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 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 Roelofs, J. J.T.H.
Right arrow Articles by Florquin, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Roelofs, J. J.T.H.
Right arrow Articles by Florquin, S.

Basic Immunology and Pathology

Tissue-Type Plasminogen Activator Modulates Inflammatory Responses and Renal Function in Ischemia Reperfusion Injury

Joris J.T.H. Roelofs*, Kasper M.A. Rouschop*, Jaklien C. Leemans*, Nike Claessen*, Anita M. de Boer{dagger}, Wilma M. Frederiks{ddagger}, H.Roger Lijnen§, Jan J. Weening* and Sandrine Florquin*

Departments of* Pathology; {dagger} Experimental Internal Medicine; {ddagger} Cell Biology and Histology, Academic Medical Center, University of Amsterdam, The Netherlands; and § Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium

Address correspondence to: Dr. Joris J.T.H. Roelofs, Department of Pathology, Room H2-131, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Phone: +31-20-5663728; Fax: +31-20-6960389; j.j.roelofs{at}amc.uva.nl

Received for publication January 21, 2005. Accepted for publication October 2, 2005.

Acute renal failure is often the result of ischemia-reperfusion (I/R) injury. Neutrophil influx is an important damaging event in I/R. Tissue-type plasminogen activator (tPA) not only is a major fibrinolytic agent but also is involved in inflammatory processes. A distinct upregulation of tPA after I/R, with de novo tPA production by proximal renal tubules, was found. For investigating the role of tPA in I/R, renal ischemia was induced in tPA–/– and wild-type (WT) mice by clamping both renal arteries for 35 min followed by reperfusion. Mice were killed 1, 5, and 10 d after reperfusion. After 1 d, tPA–/– mice displayed significantly less neutrophil influx into the interstitial area compared with WT mice. In addition, tPA–/– mice showed quicker recovery of renal function than WT mice. The protocol was repeated after injection of tPA-antisense oligonucleotides into WT mice, leading to even more explicit results: Antisense-treated mice showed less histologic damage, better renal function, and less neutrophil influx than control mice. Surprising, complement C3 concentration, levels of proinflammatory cytokines and chemokines, intercellular adhesion molecule-1 expression, and matrix metalloproteinase activity were similar in WT and tPA–/– mice. Plasmin activity levels in WT and tPA–/– kidneys were also comparable, indicating that tPA influences neutrophil influx into ischemic renal tissue independent from plasmin generation. This study shows that targeting tPA could be of therapeutic importance in treating I/R injury by diminishing neutrophil influx and preserving renal function.




This article has been cited by other articles:


Home page
 Nephrol Dial TransplantHome page
J. J. T. H. Roelofs, K. M. A. Rouschop, G. J. D. Teske, G. T. M. Wagenaar, N. Claessen, J. J. Weening, T. van der Poll, and S. Florquin
Endogenous tissue-type plasminogen activator is protective during ascending urinary tract infection
Nephrol. Dial. Transplant., October 8, 2008; (2008) gfn562v1.
[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
 J. Am. Soc. Nephrol.Home page
K. Hu, L. Lin, X. Tan, J. Yang, G. Bu, W. M. Mars, and Y. Liu
tPA Protects Renal Interstitial Fibroblasts and Myofibroblasts from Apoptosis
J. Am. Soc. Nephrol., March 1, 2008; 19(3): 503 - 514.
[Abstract] [Full Text] [PDF]

Home page
 Nephrol Dial TransplantHome page
P. Meier, J. Rossert, P.-F. Plouin, and M. Burnier
Atherosclerotic renovascular disease: beyond the renal artery stenosis
Nephrol. Dial. Transplant., April 1, 2007; 22(4): 1002 - 1006.
[Full Text] [PDF]

Home page
 J. Immunol.Home page
R. Renckens, J. J. T. H. Roelofs, S. Florquin, A. F. de Vos, J. M. Pater, H. R. Lijnen, P. Carmeliet, C. van 't Veer, and T. van der Poll
Endogenous Tissue-Type Plasminogen Activator Is Protective during Escherichia coli-Induced Abdominal Sepsis in Mice
J. Immunol., July 15, 2006; 177(2): 1189 - 1196.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
P. Devarajan
Update on Mechanisms of Ischemic Acute Kidney Injury
J. Am. Soc. Nephrol., June 1, 2006; 17(6): 1503 - 1520.
[Full Text] [PDF]


HOME CURRENT ISSUE ARCHIVES JASN Express ONLINE SUBMISSION AUTHOR INFO
EDITORIAL BOARD SUBSCRIBE FEEDBACK ALERTS HELP

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673