Starossom, S.; Mascanfroni, I.; Imitola, J.; Cao, L.; Raddassi, K.; Hernandez, S.; Bassil, R.; Croci, D.; Cerliani, J.; Delacour, D.; Wang, Y.; Elyaman, W.; Khoury, S.; Rabinovich, G. "Galectin-1 Deactivates Classically Activated Microglia and Protects from Inflammation-Induced Neurodegeneration" (2012) Immunity. 37(2):249-263
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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. © 2012 Elsevier Inc.


Documento: Artículo
Título:Galectin-1 Deactivates Classically Activated Microglia and Protects from Inflammation-Induced Neurodegeneration
Autor:Starossom, S.; Mascanfroni, I.; Imitola, J.; Cao, L.; Raddassi, K.; Hernandez, S.; Bassil, R.; Croci, D.; Cerliani, J.; Delacour, D.; Wang, Y.; Elyaman, W.; Khoury, S.; Rabinovich, G.
Filiación:Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, United States
Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires 1428, Argentina
Department of Neurobiology, Institute of Neurosciences, Second Military Medical University, Shanghai 200433, China
Department of Developmental Biology, Institut Jacques Monod, CNRS 7592, Paris-Diderot University, 75205 Paris, France
Abu Haidar Neuroscience Institute, American University of Beirut, Beirut 1107 2020, Lebanon
Laboratorio de Glicómica Funcional, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires 1428, Argentina
Palabras clave:CD45 antigen; CD86 antigen; cyclic AMP responsive element binding protein; galectin 1; gamma interferon; glycan; immunoglobulin enhancer binding protein; inducible nitric oxide synthase; interleukin 17; interleukin 4; major histocompatibility antigen class 2; mitogen activated protein kinase p38; monocyte chemotactic protein 1; phosphatase; recombinant galectin 1; recombinant protein; transforming growth factor beta1; tumor necrosis factor; unclassified drug; acute phase response; adoptive transfer; allergic encephalomyelitis; animal cell; animal experiment; animal model; animal tissue; antiinflammatory activity; article; astrocyte; cell surface; central nervous system; controlled study; demyelination; enzyme activation; enzyme activity; female; flow cytometry; inflammation; macrophage activation; microglia; mouse; nerve degeneration; neuropathy; neuroprotection; neurotoxicity; newborn; nonhuman; priority journal; protein binding; protein carbohydrate interaction; protein expression; protein function; signal transduction; Animals; Antigens, CD45; Astrocytes; Central Nervous System; Chemokine CCL2; Cyclic AMP Response Element-Binding Protein; Encephalomyelitis, Autoimmune, Experimental; Female; Galectin 1; Humans; Interleukin-6; Mice; Mice, Inbred C57BL; Mice, Knockout; Microglia; Multiple Sclerosis; NF-kappa B; Nitric Oxide Synthase Type II; p38 Mitogen-Activated Protein Kinases; Polysaccharides; Protein Binding; Tumor Necrosis Factor-alpha
Página de inicio:249
Página de fin:263
Título revista:Immunity
Título revista abreviado:Immunity
CAS:cyclic AMP responsive element binding protein, 130428-87-4, 130939-96-7; galectin 1, 258495-34-0; gamma interferon, 82115-62-6; inducible nitric oxide synthase, 501433-35-8; phosphatase, 9013-05-2; Antigens, CD45,; Chemokine CCL2; Cyclic AMP Response Element-Binding Protein; Galectin 1; Interleukin-6; NF-kappa B; Nitric Oxide Synthase Type II,; Polysaccharides; Tumor Necrosis Factor-alpha; p38 Mitogen-Activated Protein Kinases,


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---------- APA ----------
Starossom, S., Mascanfroni, I., Imitola, J., Cao, L., Raddassi, K., Hernandez, S., Bassil, R.,..., Rabinovich, G. (2012) . Galectin-1 Deactivates Classically Activated Microglia and Protects from Inflammation-Induced Neurodegeneration. Immunity, 37(2), 249-263.
---------- CHICAGO ----------
Starossom, S., Mascanfroni, I., Imitola, J., Cao, L., Raddassi, K., Hernandez, S., et al. "Galectin-1 Deactivates Classically Activated Microglia and Protects from Inflammation-Induced Neurodegeneration" . Immunity 37, no. 2 (2012) : 249-263.
---------- MLA ----------
Starossom, S., Mascanfroni, I., Imitola, J., Cao, L., Raddassi, K., Hernandez, S., et al. "Galectin-1 Deactivates Classically Activated Microglia and Protects from Inflammation-Induced Neurodegeneration" . Immunity, vol. 37, no. 2, 2012, pp. 249-263.
---------- VANCOUVER ----------
Starossom, S., Mascanfroni, I., Imitola, J., Cao, L., Raddassi, K., Hernandez, S., et al. Galectin-1 Deactivates Classically Activated Microglia and Protects from Inflammation-Induced Neurodegeneration. Immunity. 2012;37(2):249-263.