Pepro Tech
A more recent version of this article appeared on July 1, 2008

Published online before print April 7, 2008
This Article
Right arrow Full Text (Reprint (PDF))
Right arrow All Versions of this Article:
jlb.0907606v1
84/1/207    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 Cuadrado, E.
Right arrow Articles by Montaner, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cuadrado, E.
Right arrow Articles by Montaner, J.
© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0907606

Received for publication September 6, 2007.
Revised February 18, 2008.
Accepted for publication March 5, 2008.

Article

Tissue plasminogen activator (t-PA) promotes neutrophil degranulation and MMP-9 release

Eloy Cuadrado *, Laura Ortega *, Mar Hernández-Guillamon *, Anna Penalba *, Israel Fernández-Cadenas *, Anna Rosell *{dagger}, and Joan Montaner *@

*Neurovascular Research Laboratory, Neurovascular Unit, Department of Neurology, Universitat Autònoma de Barcelona, Institut de Recerca, Hospital Vall d’Hebron, Barcelona, Spain; and {dagger}Neuroprotection Research Laboratory, Department of Radiology, Massachusetts General Hospital, and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts, USA

@ To whom correspondence should be addressed. E-mail: 31862jmv{at}comb.es.


arrow
Abstract

Recombinant tissue plasminogen activator (t-PA), the only approved stroke treatment, is used for clot lysis within the occluded brain artery. Unfortunately, matrix metalloproteinase-9 (MMP-9) concentration increases after t-PA treatment and has been related to hemorrhagic transformation after ischemic stroke. Although the exact cellular source of brain MMP-9 remains unknown, invading, inflammatory cells, such as neutrophils, release MMP-9 to cross the blood brain barrier. Therefore, we hypothesize that the most feared side effect of stroke reperfusion therapy, brain hemorrhage, is related to t-PA-induced MMP-9 release by neutrophils. We show by means of ELISA that t-PA treatment promotes MMP-9, MMP-8, and tissue inhibitor metalloproteinase-2 release from human neutrophils ex vivo within 10 and 30 min. Moreover, by zymography and Western blot, we observed that neutrophils are emptied of MMP-9 content after t-PA treatment at those times. Finally, total internal reflection fluorescent imaging allowed us to observe the t-PA effect on neutrophils, showing the promotion of degranulation on these cells in vivo. Our data suggest that neutrophils are good candidates to be the main source of MMP-9 following t-PA stroke treatment and in consequence, partially responsible for thrombolysis-related brain bleedings.

Key Words: stroke • hemorrhage • TIRF • TIMP-2 • plasmin




This article has been cited by other articles:


Home page
 StrokeHome page
T. L. Barr, L. L. Latour, K.-Y. Lee, T. J. Schaewe, M. Luby, G. S. Chang, Z. El-Zammar, S. Alam, J. M. Hallenbeck, C. S. Kidwell, et al.
Blood-Brain Barrier Disruption in Humans Is Independently Associated With Increased Matrix Metalloproteinase-9
Stroke, March 1, 2010; 41(3): e123 - e128.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
B. W. McColl, N. J. Rothwell, and S. M. Allan
Systemic Inflammation Alters the Kinetics of Cerebrovascular Tight Junction Disruption after Experimental Stroke in Mice
J. Neurosci., September 17, 2008; 28(38): 9451 - 9462.
[Abstract] [Full Text] [PDF]