Your browser doesn't support javascript.
loading
Pharmacological targeting of coagulation factor XI attenuates experimental autoimmune encephalomyelitis in mice.
Kohs, Tia C L; Fallon, Meghan E; Oseas, Ethan C; Healy, Laura D; Tucker, Erik I; Gailani, David; McCarty, Owen J T; Vandenbark, Arthur A; Offner, Halina; Verbout, Norah G.
Afiliación
  • Kohs TCL; Department of Biomedical Engineering, Oregon Health & Science University, 3303 S. Bond Avenue, Portland, OR, 97239, USA. kohst@ohsu.edu.
  • Fallon ME; Department of Biomedical Engineering, Oregon Health & Science University, 3303 S. Bond Avenue, Portland, OR, 97239, USA.
  • Oseas EC; Department of Biomedical Engineering, Oregon Health & Science University, 3303 S. Bond Avenue, Portland, OR, 97239, USA.
  • Healy LD; Department of Biomedical Engineering, Oregon Health & Science University, 3303 S. Bond Avenue, Portland, OR, 97239, USA.
  • Tucker EI; Department of Biomedical Engineering, Oregon Health & Science University, 3303 S. Bond Avenue, Portland, OR, 97239, USA.
  • Gailani D; Aronora, Inc., Portland, OR, USA.
  • McCarty OJT; Department of Pathology and Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • Vandenbark AA; Department of Biomedical Engineering, Oregon Health & Science University, 3303 S. Bond Avenue, Portland, OR, 97239, USA.
  • Offner H; Department of Neurology, Oregon Health & Science University, Portland, OR, USA.
  • Verbout NG; Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, OR, USA.
Metab Brain Dis ; 38(7): 2383-2391, 2023 10.
Article en En | MEDLINE | ID: mdl-37341855
Multiple sclerosis (MS) is the most common causes of non-traumatic disability in young adults worldwide. MS pathophysiologies include the formation of inflammatory lesions, axonal damage and demyelination, and blood brain barrier (BBB) disruption. Coagulation proteins, including factor (F)XII, can serve as important mediators of the adaptive immune response during neuroinflammation. Indeed, plasma FXII levels are increased during relapse in relapsing-remitting MS patients, and previous studies showed that reducing FXII levels was protective in a murine model of MS, experimental autoimmune encephalomyelitis (EAE). Our objective was to determine if pharmacological targeting of FXI, a major substrate of activated FXII (FXIIa), improves neurological function and attenuates CNS damage in the setting of EAE. EAE was induced in male mice using murine myelin oligodendrocyte glycoprotein peptides combined with heat-inactivated Mycobacterium tuberculosis and pertussis toxin. Upon onset of symptoms, mice were treated every other day intravenously with anti-FXI antibody, 14E11, or saline. Disease scores were recorded daily until euthanasia for ex vivo analyses of inflammation. Compared to the vehicle control, 14E11 treatment reduced the clinical severity of EAE and total mononuclear cells, including CD11b+CD45high macrophage/microglia and CD4+ T cell numbers in brain. Following pharmacological targeting of FXI, BBB disruption was reduced, as measured by decreased axonal damage and fibrin(ogen) accumulation in the spinal cord. These data demonstrate that pharmacological inhibition of FXI reduces disease severity, immune cell migration, axonal damage, and BBB disruption in mice with EAE. Thus, therapeutic agents targeting FXI and FXII may provide a useful approach for treating autoimmune and neurologic disorders.
Asunto(s)
Palabras clave

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Encefalomielitis Autoinmune Experimental / Esclerosis Múltiple Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Metab Brain Dis Asunto de la revista: CEREBRO / METABOLISMO Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Encefalomielitis Autoinmune Experimental / Esclerosis Múltiple Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Metab Brain Dis Asunto de la revista: CEREBRO / METABOLISMO Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos