Artículo
Galectin-1 Deactivates Classically Activated Microglia and Protects from Inflammation-Induced Neurodegeneration
Starossom, Sarah C.; Mascanfroni, Ivan Darío
; Imitola, Jaime; Cao, Li; Raddassi, Khadir; Hernandez, Silvia Fátima
; Bassil, Ribal; Croci Russo, Diego Omar
; Cerliani, Juan Pablo
; Delacour, Delphine; Wang, Yue; Elyaman, Wassim; Khoury, Samia J.; Rabinovich, Gabriel Adrián





Fecha de publicación:
08/2012
Editorial:
Cell Press
Revista:
Immunity
ISSN:
1074-7613
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Inflammation-mediated neurodegeneration occurs in the acute and the chronic phases of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Classically activated (M1) microglia are key players mediating this process. Here, we identified Galectin-1 (Gal1), an endogenous glycan-binding protein, as a pivotal regulator of M1 microglial activation that targets the activation of p38MAPK-, CREB-, and NF-κB-dependent signaling pathways and hierarchically suppresses downstream proinflammatory mediators, such as iNOS, TNF, and CCL2. Gal1 bound to core 2 O-glycans on CD45, favoring retention of this glycoprotein on the microglial cell surface and augmenting its phosphatase activity and inhibitory function. Gal1 was highly expressed in the acute phase of EAE, and its targeted deletion resulted in pronounced inflammation-induced neurodegeneration. Adoptive transfer of Gal1-secreting astrocytes or administration of recombinant Gal1 suppressed EAE through mechanisms involving microglial deactivation. Thus, Gal1-glycan interactions are essential in tempering microglial activation, brain inflammation, and neurodegeneration, with critical therapeutic implications for MS.
Palabras clave:
GALECTIN-1
,
MICROGLIA
,
INFLAMMATION
,
NEURODEGENERATION
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Articulos(IBYME)
Articulos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)
Articulos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)
Citación
Starossom, Sarah C.; Mascanfroni, Ivan Darío; Imitola, Jaime; Cao, Li; Raddassi, Khadir; et al.; Galectin-1 Deactivates Classically Activated Microglia and Protects from Inflammation-Induced Neurodegeneration; Cell Press; Immunity; 37; 2; 8-2012; 249-263
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