Abstract
Introduction. Glutamate receptors are involved in modulating key T-lymphocyte functions, including proliferation, chemotaxis, and others. In the context of the immunopathogenesis of multiple sclerosis (MS), studying the mechanisms underlying these effects is of great scientific and practical interest.
The aim of the study. To investigate the molecular mechanisms underlying AMPA receptors (AMPARs) in T-lymphocyte adhesion in MS.
Material and methods. The study involved peripheral blood lymphocytes from healthy donors and MS patients. The effects of AMPAR glutamate agonists and antagonists on T-cell adhesion were determined using human umbilical vein endothelial cells as an in vitro model of the blood-brain barrier. The effect of glutamate AMPAR receptor ligands on the expression of the adhesion molecule VLA-4 (Very late antigen-4) by various T-helper cell subsets was studied using flow cytometry.
Results. According to the study results, cells from MS patients in the acute stage were most sensitive to the effects of glutamate AMPAR ligands. Their action resulted in changes in the level of T-cell adhesion to endothelial cells, as well as in the surface expression of the key adhesion molecule VLA-4. Importantly, the NBQX antagonist inhibited VLA-4 expression primarily in subsets of T-helper cells types 1, 17, and 17.1. The observed heterogeneity in the response of T-lymphocyte subsets likely reflects differences in sensitivity to the functional state of AMPA receptors or the involvement of cells in the adhesion process.
Conclusion. AMPA glutamate receptors have been shown to be involved in modulating the adhesion of T-lymphocyte subsets pathogenetically significant for MS. The importance of this glutamate receptor subtype increases during disease exacerbation. These identified functional features of glutamate neurotransmitter receptors contribute to our understanding of the pathogenesis of MS and the development of new approaches to pharmacotherapy.
Authors and affiliations
https://elibrary.ru/rluwwb
A.V. Tukhvatullin(1), U.S. Kuzmina(1, 2), K.Z. Bakhtiyarova(2), Yu.V. Vakhitova(1)
1-Institute of Biochemistry and Genetics – a separate structural subdivision of the Federal State Budgetary Scientific Institution Ufa
Federal Research Centre of the Russian Academy of Sciences, Oktyabrya Avenue, 71, Ufa, 450054, Russian Federation; 2-Federal State
Budgetary Educational Institution of Higher Education “Bashkir State Medical University”, Ministry of Health of the Russian Federation,
Lenin St., 3, Ufa, 450008, Russian Federation
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