INVESTIGADORES
CROCI RUSSO Diego Omar
artículos
Título:
GALECTIN-1 DEACTIVATES CLASSICALLY ACTIVATED MICROGLIA AND PROTECTS FROM INFLAMMATION-INDUCED NEURODEGENERATION
Autor/es:
STAROSSOM SC; MASCANFRONI ID; IMITOLA J; CAO L; RADDASSI KS; HERNANDEZ F; BASSIL RE; CROCI DO; CERLIANI JP; DELACOUR D; WANG Y; ELYAMAN W; KHOURY SJ; G. A.RABINOVICH
Revista:
IMMUNITY
Editorial:
CELL PRESS
Referencias:
Lugar: United States; Año: 2012 vol. 37 p. 249 - 263
ISSN:
1074-7613
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-kB-depen-
dent signaling pathways and hierarchically sup-
presses 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 aug-
menting its phosphatase activity and inhibitory func-
tion. Gal1 was highly expressed in the acute phase
of EAE, and its targeted deletion resulted in pro-
nounced inflammation-induced neurodegeneration.
Adoptive transfer of Gal1-secreting astrocytes or ad-
ministration of recombinant Gal1 suppressed EAE
through mechanisms involving microglial deactiva-
tion. Thus, Gal1-glycan interactions are essential in
tempering microglial activation, brain inflammation,
and neurodegeneration, with critical therapeutic im-
plications for MS.