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Targeting Mannose-Binding Lectin Confers Long-Lasting Protection With a Surprisingly Wide Therapeutic Window in Cerebral Ischemia

Circulation (New York, N.Y.), 2012-09, Vol.126 (12), p.1484-1494 [Peer Reviewed Journal]

2015 INIST-CNRS ;ISSN: 0009-7322 ;EISSN: 1524-4539 ;DOI: 10.1161/CIRCULATIONAHA.112.103051 ;PMID: 22879370 ;CODEN: CIRCAZ

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Title:
Targeting Mannose-Binding Lectin Confers Long-Lasting Protection With a Surprisingly Wide Therapeutic Window in Cerebral Ischemia
Author: ORSINI, Franca ; VILLA, Pia ; PALADINI, Alessandra ; MICOTTI, Edoardo ; RIBEIRO-VIANA, Renato ; ROJO, Javier ; PAVLOV, Vasile I ; STAHL, Gregory L ; BERNARDI, Anna ; GOBBI, Marco ; DE SIMONI, Maria-Grazia ; PARRELLA, Sara ; ZANGARI, Rosalia ; ZANIER, Elisa R ; GESUETE, Raffaella ; STRAVALACI, Matteo ; FUMAGALLI, Stefano ; OTTRIA, Roberta ; REINA, Jose J
Subjects: Animals ; Antibodies, Monoclonal - pharmacology ; Biological and medical sciences ; Blood and lymphatic vessels ; Brain Edema - drug therapy ; Brain Edema - genetics ; Brain Edema - physiopathology ; Brain Ischemia - drug therapy ; Brain Ischemia - genetics ; Brain Ischemia - physiopathology ; Cardiology. Vascular system ; Disease Models, Animal ; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous ; Humans ; Infarction, Middle Cerebral Artery - drug therapy ; Infarction, Middle Cerebral Artery - genetics ; Infarction, Middle Cerebral Artery - physiopathology ; Investigative techniques, diagnostic techniques (general aspects) ; Male ; Mannans - metabolism ; Mannans - pharmacology ; Mannose-Binding Lectin - genetics ; Mannose-Binding Lectin - immunology ; Mannose-Binding Lectin - metabolism ; Medical sciences ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Nervous system ; Radiodiagnosis. Nmr imagery. Nmr spectrometry ; Rats ; Rats, Inbred Strains
Is Part Of: Circulation (New York, N.Y.), 2012-09, Vol.126 (12), p.1484-1494
Description: 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. 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. 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.
Publisher: Hagerstown, MD: Lippincott Williams & Wilkins
Language: English
Identifier: ISSN: 0009-7322
EISSN: 1524-4539
DOI: 10.1161/CIRCULATIONAHA.112.103051
PMID: 22879370
CODEN: CIRCAZ
Source: GFMER Free Medical Journals
MEDLINE

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Targeting Mannose-Binding Lectin Confers Long-Lasting Protection With a Surprisingly Wide Therapeutic Window in Cerebral Ischemia

2015 INIST-CNRS ;ISSN: 0009-7322 ;EISSN: 1524-4539 ;DOI: 10.1161/CIRCULATIONAHA.112.103051 ;PMID: 22879370 ;CODEN: CIRCAZ

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