Antagonizing the alpha(4)beta(1) Integrin, but Not alpha(4)beta(7), Inhibits Leukocytic Infiltration of the Central Nervous System in Rhesus Monkey Experimental Autoimmune Encephalomyelitis

Autor: Krista G. Haanstra, Erwin L. A. Blezer, Tim Wyant, Vilmos Csizmadia, Sam O. Hofman, Li-Li Yang, Dave M. Lopes Estevao, Eric R. Fedyk, Jan Bauer, Bert A. 't Hart
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Central Nervous System
Encephalomyelitis
Autoimmune
Experimental
T-Lymphocytes
Immunology
Integrin
Central nervous system
PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY
Autoimmunity
Integrin alpha4beta1
Antibodies
Monoclonal
Humanized
EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS
PLACEBO-CONTROLLED TRIAL
CELL-ADHESION MOLECULE-1
Vedolizumab
Myelin oligodendrocyte glycoprotein
Placebos
Natalizumab
Immune system
Cell Movement
MEMORY T-CELLS
MYELIN OLIGODENDROCYTE GLYCOPROTEIN
medicine
Animals
Humans
Protein Isoforms
Immunology and Allergy
Immunologic Surveillance
biology
BLOOD-BRAIN-BARRIER
Experimental autoimmune encephalomyelitis
medicine.disease
Macaca mulatta
ACTIVE CROHNS-DISEASE
Recombinant Proteins
medicine.anatomical_structure
Organ Specificity
Cell Migration Inhibition
Injections
Intravenous
NONHUMAN PRIMATE MODELS
biology.protein
Tissue tropism
Myelin-Oligodendrocyte Glycoprotein
RELAPSING MULTIPLE-SCLEROSIS
medicine.drug
Zdroj: Journal of Immunology, 190(5), 1961-1973. AMER ASSOC IMMUNOLOGISTS
ISSN: 0022-1767
Popis: The immune system is characterized by the preferential migration of lymphocytes through specific tissues (i.e., tissue tropism). Tissue tropism is mediated, in part, by the alpha(4) integrins expressed by T lymphocytes. The alpha(4)beta(1) integrin mediates migration of memory T lymphocytes into the CNS, whereas the alpha(4)beta(7) integrin mediates migration preferentially into gastrointestinal tissue. This paradigm was established primarily from investigations in rodents; thus, the objective of this investigation was to determine if blocking the alpha(4)beta(7) integrin exclusively would affect migration of T lymphocytes into the CNS of primates. The effects of the dual alpha(4)beta(1) and alpha(4)beta(7) antagonist natalizumab were compared with those of the alpha(4)beta(7) antagonist vedolizumab on experimental autoimmune encephalomyelitis in the rhesus monkey. Animals received an initial i.v. bolus of placebo, natalizumab (30 mg/kg), or vedolizumab (30 mg/kg) before intracutaneous immunization with recombinant human myelin oligodendrocyte glycoprotein and then Ab once weekly thereafter. Natalizumab prevented CNS inflammation and demyelination significantly (p
Databáze: OpenAIRE
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