scholarly journals Platelet Inhibition by Low-Dose Acetylsalicylic Acid Reduces Neuroinflammation in an Animal Model of Multiple Sclerosis

2021 ◽  
Vol 22 (18) ◽  
pp. 9915
Author(s):  
Anna Vogelsang ◽  
Susann Eichler ◽  
Niklas Huntemann ◽  
Lars Masanneck ◽  
Hannes Böhnlein ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Acetylsalicylic Acid ◽  
Low Dose ◽  
Antiplatelet Agent ◽  
Adaptive Immune Response ◽  
Platelet Inhibition ◽  
Platelet Factor ◽  
Glycoprotein Vi ◽  
Inflammatory Infiltrates

Aside from the established immune-mediated etiology of multiple sclerosis (MS), compelling evidence implicates platelets as important players in disease pathogenesis. Specifically, numerous studies have highlighted that activated platelets promote the central nervous system (CNS)-directed adaptive immune response early in the disease course. Platelets, therefore, present a novel opportunity for modulating the neuroinflammatory process that characterizes MS. We hypothesized that the well-known antiplatelet agent acetylsalicylic acid (ASA) could inhibit neuroinflammation by affecting platelets if applied at low-dose and investigated its effect during experimental autoimmune encephalomyelitis (EAE) as a model to study MS. We found that oral administration of low-dose ASA alleviates symptoms of EAE accompanied by reduced inflammatory infiltrates and less extensive demyelination. Remarkably, the percentage of CNS-infiltrated CD4+ T cells, the major drivers of neuroinflammation, was decreased to 40.98 ± 3.28% in ASA-treated mice compared to 56.11 ± 1.46% in control animals at the disease maximum as revealed by flow cytometry. More interestingly, plasma levels of thromboxane A2 were decreased, while concentrations of platelet factor 4 and glycoprotein VI were not affected by low-dose ASA treatment. Overall, we demonstrate that low-dose ASA could ameliorate the platelet-dependent neuroinflammatory response in vivo, thus indicating a potential treatment approach for MS.

Functions of Platelet Microparticles in Inflammatory Arthritis

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. SCI-35-SCI-35
Author(s):  
Nathalie Cloutier ◽  
Richard W. Farndale ◽  
Alain Brisson ◽  
Eric Boilard
Keyword(s):  
Wound Repair ◽  
Inflammatory Responses ◽  
Conflicts Of Interest ◽  
Adenosine Diphosphate ◽  
Submicron Particles ◽  
Synovial Joint ◽  
Platelet Factor ◽  
Glycoprotein Vi ◽  
Platelet Microparticles

Abstract Abstract SCI-35 Besides their pivotal role in thrombosis and wound repair, platelets can participate in inflammatory responses via a broad arsenal that includes CD40L and CD40, cyclooxygenase-1 mediated prostaglandins, leukotrienes, IL-1, RANTES, serotonin, platelet factor 4, matrix metalloproteinases -2 and -9, P-selectin, adenosine diphosphate, and reactive oxygen species. Rheumatoid arthritis (RA) is amongst the most common autoimmune chronic inflammation that affects the joints. Interestingly, we found copious amounts of submicron particles that harbor platelet integrins in the synovial fluid of patients suffering from RA, pointing to evidence of platelet activation in this inflammatory autoimmune disease. Importantly, we identified the collagen receptor glycoprotein VI as a key trigger for platelet microparticle generation in arthritis pathophysiology. In addition to the transcellular collaboration between platelets and fibroblast-like synoviocytes in generation of pro-inflammatory prostacyclin (1), we found that platelets contribute to synovitis by production of IL-1-rich platelet microparticles (2). These recent advances in understanding of the platelet activities in inflammation notwithstanding, the mechanisms by which platelet microparticles invade the diseased joint in RA remain obscure. Using synovial biopsies from patients suffering from RA in addition to in vivo imaging strategies in a murine model of arthritis, our current work aspires to dissect the means of transportation of platelet microparticles during RA. Given their pro-inflammatory properties, to understand the process by which microparticles invade the synovial joint is of great clinical interest. Disclosures: No relevant conflicts of interest to declare.

Low dose acetylsalicylic acid and shedding of microparticles in vivo in humans

2010 ◽  
Vol 40 (6) ◽  
pp. 477-482 ◽  
Author(s):  
Barbara Lubsczyk ◽  
Marietta Kollars ◽  
Gregor Hron ◽  
Paul A Kyrle ◽  
Ansgar Weltermann ◽  
...  
Keyword(s):  
Acetylsalicylic Acid ◽  
Low Dose

scholarly journals In Vivo Survival of  Viral Antigen–specific T Cells that Induce Experimental Autoimmune Encephalomyelitis

1998 ◽  
Vol 188 (9) ◽  
pp. 1725-1738 ◽  
Author(s):  
Rafael L. Ufret-Vincenty ◽  
Laura Quigley ◽  
Nancy Tresser ◽  
Seong Hee Pak ◽  
Ameer Gado ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
T Cell ◽  
Viral Antigen ◽  
Low Dose ◽  
Cell Clone ◽  
Viral Peptide ◽  
Autoreactive T Cell ◽  
T Cell Clone

A peptide derived from the human papillomavirus L2 protein is recognized by a myelin basic protein (MBP)-specific T cell clone from a multiple sclerosis patient and by MBP-specific autoantibodies purified from multiple sclerosis brain tissue. We now show in mice that low doses of this papillomavirus peptide were optimal in selecting a subpopulation of papillomavirus peptide–specific T cells that cross-reacted with MBP(87–99) and with an unrelated viral peptide derived from the BSLF1 protein of Epstein-Barr virus (EBV). These low dose viral peptide– specific T cell lines were highly encephalitogenic. Splenocytes from mice transferred with viral peptide–specific T cells showed a vigorous response to both the papillomavirus and MBP peptides, indicating that viral antigen–specific T cells survived for a prolonged time in vivo. The EBV peptide, unable to prime and select an autoreactive T cell population, could still activate the low dose papillomavirus peptide–specific cells and induce central nervous system (CNS) autoimmunity. Cytokine profiles of papillomavirus peptide–specific encephalitogenic T cells and histopathology of CNS lesions resembled those induced by MBP. These results demonstrate conserved aspects in the recognition of the self-antigen and a cross-reactive viral peptide by human and murine MBP-specific T cell receptors. We demonstrate that a viral antigen, depending on its nature, dose, and number of exposures, may select autoantigen-specific T cells that survive in vivo and can trigger autoimmune disease after adoptive transfer.

Low-Dose Acetylsalicylic Acid Reduces Hepatic Proliferation In Vivo But Not In Vitro

1989 ◽  
Vol 76 (s20) ◽  
pp. 9P-9P
Author(s):  
A.C. Woodman ◽  
D.A. Vesey ◽  
A.C. Selden ◽  
H.J.H. Hodgson
Keyword(s):  
Acetylsalicylic Acid ◽  
Low Dose

Scutellarin Suppresses Platelet Aggregation and Stalls Lesional Progression in Mouse With Induced Endometriosis

2018 ◽  
Vol 26 (11) ◽  
pp. 1417-1428 ◽  
Author(s):  
Ding Ding ◽  
Xianjun Cai ◽  
Hanxi Zheng ◽  
Sun-Wei Guo ◽  
Xishi Liu
Keyword(s):  
Platelet Aggregation ◽  
Low Dose ◽  
Cellular Proliferation ◽  
Antiplatelet Agent ◽  
Lesion Size ◽  
High Dose ◽  
Activated Platelets ◽  
Activation Rate ◽  
Before And After

Platelets play an important role in the development of endometriosis. Scutellarin is a flavonoid isolated from a medicinal herb traditionally used as a potent antiplatelet agent. In this study, we sought to evaluate its potential therapeutic effect, if any, in mice with induced endometriosis. Endometriosis was induced in 27 female Balb/c mice by intraperitoneal injection of uterine fragments. Two weeks after the induction, the 27 mice were randomly divided in equal sizes into 3 groups: untreated, which received only vehicle, and low-dose and high-dose groups, which received low- and high dose of scutellarin treatment. Hotplate test was administrated to all mice before endometriosis induction, and before and after the scutellarin treatment. Two weeks after the treatment, a blood sample was drawn before sacrifice and all lesions were harvested. The peripheral platelet activation rate and total lesion weight were assessed, and immunohistochemistry and histochemistry analyses were performed to evaluate the extent of proliferation, angiogenesis, fibroblast-to-myofibroblast transdifferentiation (FMT), and fibrosis in lesions. Compared with untreated mice, mice in both low-dose and high-dose groups had significantly reduced lesion weight and improved hyperalgesia. Scutellarin also reduced the peripheral-activated platelets rate and resulted in significantly reduced platelet aggregation, cellular proliferation, angiogenesis, the extent of FMT, and the extent of fibrosis in lesions. Thus, we conclude that scutellarin is efficacious in treating endometriosis in vivo by suppressing platelet aggregation, inhibiting proliferation, angiogenesis, and fibrogenesis, resulting in reduced lesion size and improved pain behavior. As such, scutellarin may be a potentially promising therapeutics for the treatment of endometriosis.

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