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.
journal_name
J Leukoc Bioljournal_title
Journal of leukocyte biologyauthors
Cuadrado E,Ortega L,Hernández-Guillamon M,Penalba A,Fernández-Cadenas I,Rosell A,Montaner Jdoi
10.1189/jlb.0907606subject
Has Abstractpub_date
2008-07-01 00:00:00pages
207-14issue
1eissn
0741-5400issn
1938-3673pii
jlb.0907606journal_volume
84pub_type
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