Platelets in Multiple Sclerosis: Early and Central Mediators of Inflammation and Neurodegeneration and Attractive Targets for Molecular Imaging and Site-Directed Therapy

Frontiers in Immunology

Claretta S. D'Souza²  Jacqueline M. Orian²  Karlheinz Peter⁴  Xiaowei Wang⁴  Pece Kocovski⁵  Matthew W. Hale⁵  Guy Krippner⁶ 

[1] Atherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia;Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC, Australia;Department of Cardiometabolic Health, University of Melbourne, Melbourne, VIC, Australia;Department of Physiology, Anatomy and Microbiology, School of Life Science, La Trobe University, Melbourne, VIC, Australia;Department of Psychology and Counselling, School of Psychology and Public Health, College of Science, Health and Engineering, La Trobe University, Melbourne, VIC, Australia;Medicinal Chemistry, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia;Molecular Imaging and Theranostics Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia;

关键词: platelets;    multiple sclerosis;    experimental autoimmune encephalomyelitis;    neuroprotection;    neuroinflammation;    imaging;   

DOI  :  10.3389/fimmu.2021.620963

来源: DOAJ

【 摘 要 】

Platelets are clearly central to thrombosis and hemostasis. In addition, more recently, evidence has emerged for non-hemostatic roles of platelets including inflammatory and immune reactions/responses. Platelets express immunologically relevant ligands and receptors, demonstrate adhesive interactions with endothelial cells, monocytes and neutrophils, and toll-like receptor (TLR) mediated responses. These properties make platelets central to innate and adaptive immunity and potential candidate key mediators of autoimmune disorders. Multiple sclerosis (MS) is the most common chronic autoimmune central nervous system (CNS) disease. An association between platelets and MS was first indicated by the increased adhesion of platelets to endothelial cells. This was followed by reports identifying structural and functional changes of platelets, their chronic activation in the peripheral blood of MS patients, platelet presence in MS lesions and the more recent revelation that these structural and functional abnormalities are associated with all MS forms and stages. Investigations based on the murine experimental autoimmune encephalomyelitis (EAE) MS model first revealed a contribution to EAE pathogenesis by exacerbation of CNS inflammation and an early role for platelets in EAE development via platelet-neuron and platelet-astrocyte associations, through sialated gangliosides in lipid rafts. Our own studies refined and extended these findings by identifying the critical timing of platelet accumulation in pre-clinical EAE and establishing an initiating and central rather than merely exacerbating role for platelets in disease development. Furthermore, we demonstrated platelet-neuron associations in EAE, coincident with behavioral changes, but preceding the earliest detectable autoreactive T cell accumulation. In combination, these findings establish a new paradigm by asserting that platelets play a neurodegenerative as well as a neuroinflammatory role in MS and therefore, that these two pathological processes are causally linked. This review will discuss the implications of these findings for our understanding of MS, for future applications for imaging toward early detection of MS, and for novel strategies for platelet-targeted treatment of MS.

【 授权许可】

Unknown