Targeting mannose-binding lectin confers long-lasting protection with a surprisingly wide therapeutic window in cerebral ischemia
Articolo
Data di Pubblicazione:
2012
Citazione:
Targeting mannose-binding lectin confers long-lasting protection with a surprisingly wide therapeutic window in cerebral ischemia / F. Orsini, P. Villa, S. Parrella, R. Zangari, E. R. Zanier, R. Gesuete, M. Stravalaci, S. Fumagalli, R. Ottria, J.J. Reina, A. Paladini, E. Micotti, R. Ribeiro-Viana, J. Rojo, V. I. Pavlov, G. L. Stahl, A. Bernardi, M. Gobbi, M. G. De Simoni. - In: CIRCULATION. - ISSN 0009-7322. - 126:12(2012 Sep), pp. 1484-1494.
Abstract:
Abstract
BACKGROUND: The involvement of the complement system in brain injury has been scarcely investigated. Here, we document the pivotal role of mannose-binding lectin (MBL), one of the recognition molecules of the lectin complement pathway, in brain ischemic injury.
METHODS AND RESULTS: Focal cerebral ischemia was induced in mice (by permanent or transient middle cerebral artery occlusion) and rats (by 3-vessel occlusion). We first observed that MBL is deposited on ischemic vessels up to 48 hours after injury and that functional MBL/MBL-associated serine protease 2 complexes are increased. Next, we demonstrated that (1) MBL(-/-) mice are protected from both transient and permanent ischemic injury; (2) Polyman2, the newly synthesized mannosylated molecule selected for its binding to MBL, improves neurological deficits and infarct volume when given up to 24 hours after ischemia in mice; (3) anti-MBL-A antibody improves neurological deficits and infarct volume when given up to 18 hours after ischemia, as assessed after 28 days in rats.
CONCLUSIONS: Our data show an important role for MBL in the pathogenesis of brain ischemic injury and provide a strong support to the concept that MBL inhibition may be a relevant therapeutic target in humans, one with a wide therapeutic window of application
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
F. Orsini, P. Villa, S. Parrella, R. Zangari, E. R. Zanier, R. Gesuete, M. Stravalaci, S. Fumagalli, R. Ottria, J.J. Reina, A. Paladini, E. Micotti, R. Ribeiro-Viana, J. Rojo, V. I. Pavlov, G. L. Stahl, A. Bernardi, M. Gobbi, M. G. De Simoni
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