Pharmacological targeting of coagulation factor XI attenuates experimental autoimmune encephalomyelitis in mice.
EAE
Factor XI
Multiple sclerosis
Thrombin
Journal
Metabolic brain disease
ISSN: 1573-7365
Titre abrégé: Metab Brain Dis
Pays: United States
ID NLM: 8610370
Informations de publication
Date de publication:
10 2023
10 2023
Historique:
received:
15
03
2023
accepted:
05
06
2023
medline:
18
9
2023
pubmed:
21
6
2023
entrez:
21
6
2023
Statut:
ppublish
Résumé
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
Identifiants
pubmed: 37341855
doi: 10.1007/s11011-023-01251-1
pii: 10.1007/s11011-023-01251-1
pmc: PMC10530106
mid: NIHMS1929794
doi:
Substances chimiques
Factor XI
9013-55-2
Myelin-Oligodendrocyte Glycoprotein
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
2383-2391Subventions
Organisme : NHLBI NIH HHS
ID : R01HL101972
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI148409
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL101972
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI048490
Pays : United States
Organisme : NHLBI NIH HHS
ID : R35 HL140025
Pays : United States
Organisme : BLRD VA
ID : IK6 BX004209
Pays : United States
Organisme : BLRD VA
ID : I01 BX000226
Pays : United States
Organisme : NHLBI NIH HHS
ID : F31 HL162467
Pays : United States
Organisme : NHLBI NIH HHS
ID : 1F31HL162467-01A1
Pays : United States
Organisme : NIAID NIH HHS
ID : R42 AI122574
Pays : United States
Organisme : BLRD VA
ID : I01 BX005112
Pays : United States
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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