scholarly journals Platelets Disseminate Extracellular Vesicles in Lymph in Rheumatoid Arthritis

2020 ◽  
Vol 40 (4) ◽  
pp. 929-942 ◽  
Author(s):  
Nicolas Tessandier ◽  
Imene Melki ◽  
Nathalie Cloutier ◽  
Isabelle Allaeys ◽  
Adam Miszta ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Extracellular Vesicles ◽  
Lymphatic System ◽  
Circulatory System ◽  
Donor Cell ◽  
Vascular Leakage ◽  
In Vivo Model ◽  
Interstitial Tissue ◽  
Tissue Fluid

Objective: The lymphatic system is a circulatory system that unidirectionally drains the interstitial tissue fluid back to blood circulation. Although lymph is utilized by leukocytes for immune surveillance, it remains inaccessible to platelets and erythrocytes. Activated cells release submicron extracellular vesicles (EV) that transport molecules from the donor cell. In rheumatoid arthritis, EV accumulate in the joint where they can interact with numerous cellular lineages. However, whether EV can exit the inflamed tissue to recirculate is unknown. Here, we investigated whether vascular leakage that occurs during inflammation could favor EV access to the lymphatic system. Approach and Results: Using an in vivo model of autoimmune inflammatory arthritis, we show that there is an influx of platelet EV, but not EV from erythrocytes or leukocytes, in joint-draining lymph. In contrast to blood platelet EV, lymph platelet EV lacked mitochondrial organelles and failed to promote coagulation. Platelet EV influx in lymph was consistent with joint vascular leakage and implicated the fibrinogen receptor α2bβ 3 and platelet-derived serotonin. Conclusions: These findings show that platelets can disseminate their EV in fluid that is inaccessible to platelets and beyond the joint in this disease.

scholarly journals Capsaicin-Sensitive Peptidergic Sensory Nerves Are Anti-Inflammatory Gatekeepers in the Hyperacute Phase of a Mouse Rheumatoid Arthritis Model

2021 ◽  
Vol 22 (4) ◽  
pp. 1682
Author(s):  
Bálint Botz ◽  
Gábor Kriszta ◽  
Kata Bölcskei ◽  
Ádám István Horváth ◽  
Attila Mócsai ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Morphological Changes ◽  
Vascular Leakage ◽  
Sensory Nerves ◽  
Clinical Severity ◽  
Severity Scores ◽  
Clinical Scoring ◽  
Anti Inflammatory ◽  
Ros Burst

Capsaicin-sensitive peptidergic sensory nerves play complex, mainly protective regulatory roles in the inflammatory cascade of the joints via neuropeptide mediators, but the mechanisms of the hyperacute arthritis phase has not been investigated. Therefore, we studied the involvement of these afferents in the early, “black box” period of a rheumatoid arthritis (RA) mouse model. Capsaicin-sensitive fibres were defunctionalized by pretreatment with the ultrapotent capsaicin analog resiniferatoxin and arthritis was induced by K/BxN arthritogenic serum. Disease severity was assessed by clinical scoring, reactive oxygen species (ROS) burst by chemiluminescent, vascular permeability by fluorescent in vivo imaging. Contrast-enhanced magnetic resonance imaging was used to correlate the functional and morphological changes. After sensory desensitization, both early phase ROS-burst and vascular leakage were significantly enhanced, which was later followed by the increased clinical severity scores. Furthermore, the early vascular leakage and ROS-burst were found to be good predictors of later arthritis severity. We conclude that the anti-inflammatory role of peptidergic afferents depends on their activity in the hyperacute phase, characterized by decreased cellular and vascular inflammatory components presumably via anti-inflammatory neuropeptide release. Therefore, these fibres might serve as important gatekeepers in RA.

Physiological models for in vivo imaging and targeting the lymphatic system: nanoparticles and extracellular vesicles

2021 ◽  
pp. 113833
Author(s):  
David Olmeda ◽  
Daniela Cerezo-Wallis ◽  
Elena Castellano-Sanz ◽  
Susana García-Silva ◽  
Héctor Peinado ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
In Vivo Imaging ◽  
Lymphatic System ◽  
Physiological Models

scholarly journals Immune‐modulator Metallo‐peptide (IMMP) effect on an in vivo model of Rheumatoid Arthritis

2012 ◽  
Vol 26 (S1) ◽  
Author(s):  
Lourdes Rodríguez-Fragoso ◽  
Carlos A. Arjona-Canul ◽  
Jorge Reyes-Esparza
Keyword(s):  
Rheumatoid Arthritis ◽  
In Vivo Model ◽  
Immune Modulator

Bodyweight Apparatus Used to Apply Compression Garments for Lymphedema Patients

2011 ◽  
Author(s):  
David DeRoche ◽  
Zachary Sharp
Keyword(s):  
Radiation Therapy ◽  
Cancer Treatment ◽  
Interstitial Fluid ◽  
Lymphatic System ◽  
Medical Condition ◽  
Circulatory System ◽  
Interstitial Tissue ◽  
Compression Garments ◽  
Affected Area ◽  
System 1

Lymphedema is a medical condition caused by an excess of fluid collecting in the interstitial tissue. When the lymphatic system is functioning normally, the interstitial fluid passes into the lymphatic capillaries, thought the lymphatic ducts, and returns to the circulatory system [1]. If this system is disrupted due to congenital reasons, surgery, or radiation therapy associated with cancer treatment, the fluid is unable to properly drain [2]. This collection of fluid leads to swelling of the affected area, usually the legs or arms (Figure 1).

scholarly journals Potential withdrawal of rheumatoid synovium by the induction of apoptosis using a novel in vivo model of rheumatoid arthritis

1998 ◽  
Vol 41 (7) ◽  
pp. 1251-1257 ◽  
Author(s):  
Kiyoshi Sakai ◽  
Hiroaki Matsuno ◽  
ISAYA MORITA ◽  
Takeshi Nezuka ◽  
Haruo Tsuji ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
In Vivo Model ◽  
Rheumatoid Synovium ◽  
Induction Of Apoptosis

scholarly journals MicroRNA-21 from bone marrow mesenchymal stem cell-derived extracellular vesicles targets TET1 to suppress KLF4 and alleviate rheumatoid arthritis

2021 ◽  
Vol 12 ◽  
pp. 204062232110073
Author(s):  
Guo-Qing Li ◽  
Yu-Xuan Fang ◽  
Ying Liu ◽  
Fan-Ru Meng ◽  
Xia Wu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Marrow ◽  
Extracellular Vesicles ◽  
Mouse Fibroblast ◽  
Luciferase Assay ◽  
Loss Of Function ◽  
Regulatory Relationship ◽  
Dual Luciferase Assay

Background: Accumulating evidence has demonstrated that bone marrow mesenchymal stem cells (BMSCs)-derived extracellular vesicles (EVs) can be used effectively to transfer drugs and biomolecules to target lesions. Meanwhile, BMSCs have been reported to be beneficial in the treatment of rheumatoid arthritis (RA). In this study, we employ gain- and loss-of-function experiments to determine how BMSCs-derived EVs alleviate RA in vitro and in vivo. Methods: We isolated EVs from BMSCs and characterized them by transmission electron microscopy and western blot analysis. The regulatory relationship between miR-21 and TET1 was predicted by bioinformatics analysis and validated by dual luciferase assay. Next, we utilized bisulfite sequencing PCR to decipher how TET1 promoted KLF4 transcription. Then, we established an RA mouse model and determined the role of miR-21 in RA progression. Functional assays were used to validate the role the miR-21-TET1-KLF4 regulatory axis in controlling mouse fibroblast-like synoviocytes (mFLS) cell proliferation and inflammatory cytokines secretion in vitro. Results: RT-qPCR results revealed that miR-21 was highly expressed in BMSCs-derived EVs, and confirmed that BMSCs-derived EVs transferred miR-21 into mFLS cells. Bioinformatic analysis predicted that TET1 was the directly downstream target of miR-21, which was further validated by dual luciferase assay. TET1 promoted KLF4 promoter methylation to increase its expression. Collectively, BMSCs-derived EVs relieved RA by delivering miR-21, while the exosomal miR-21 alleviated RA through targeting the TET1/KLF4 regulatory axis. Conclusion: miR-21 from BMSCs-derived EVs suppresses KLF4 to relive RA by targeting TET1.

scholarly journals Regulation of lymphangiogenesis by extracellular vesicles in cancer metastasis

2021 ◽  
pp. 153537022110210
Author(s):  
Chu-An Wang ◽  
Shaw-Jenq Tsai
Keyword(s):  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Lymphatic Metastasis ◽  
Lymphatic Vessel ◽  
Cancer Metastasis ◽  
Lymphatic System ◽  
Lymphatic Vessels ◽  
Extracellular Vesicle ◽  
Tissue Fluid ◽  
Vessel Infiltration

Metastasis is not only one of the hallmarks of cancer but, unfortunately, it also is the most accurate biomarker for poor prognosis. Cancer cells metastasize through two different but eventually merged routes, the vasculature and lymphatic systems. The processes of cancer metastasis through blood vessel have been extensively studied and are well documented in the literature. In contrast, metastasis through the lymphatic system is less studied. Most people believe that cancer cells metastasize through lymphatic vessel are passive because the lymphatic system is thought to be a sewage draining system that collects whatever appears in the tissue fluid. It was recently found that cancer cells disseminated from lymphatic vessels are protected from being destroyed by our body’s defense system. Furthermore, some cancer cells or cancer-associated immune cells secrete lymphangiogenic factors to recruit lymphatic vessel infiltration to the tumor region, a process known as lymphangiogenesis. To ensure the efficiency of lymphangiogenesis, the lymphangiogenic mediators are carried or packed by nanometer-sized particles named extracellular vesicles. Extracellular vesicles are lipid bilayer particles released from eventually every single cell, including bacterium, with diameters ranging from 30 nm (exosome) to several micrometers (apoptotic body). Components carried by extracellular vesicles include but are not limited to DNA, RNA, protein, fatty acid, and other metabolites. Recent studies suggest that cancer cells not only secrete more extracellular vesicles but also upload critical mediators required for lymphatic metastasis onto extracellular vesicles. This review will summarize recent advances in cancer lymphatic metastasis and how cancer cells regulate this process via extracellular vesicle-dependent lymphangiogenesis.

scholarly journals Preparation of EGCG decorated, injectable extracellular vesicles for cartilage repair in rat arthritis

2021 ◽  
Author(s):  
Changwei Song ◽  
Shibo Xu ◽  
Linna Chang ◽  
Xingjun Zhao ◽  
Xifan Mei ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Extracellular Vesicles ◽  
Animal Experiments ◽  
Measurement Data ◽  
Type Ii Collagen ◽  
Type Ii ◽  
Egcg Treatment ◽  
Limited Mobility

Abstract Arthritis is a kind of chronic inflammatory autoimmune disease, which can destroy joint cartilage and bone, leading to joint pain, joint swelling, and limited mobility. Traditional therapies have many side effects or focus too much on anti-inflammation while neglecting joint repair. In this experiment, we combined EGCG (Epigallocatechin gallate) with extracellular vesicles derived from macrophages to treat rheumatoid arthritis. Sustained-release resulted in a significant decrease in chondrocyte expression of HIF-1α, a decrease in apoptosis-related proteins Cytochrome C, Caspase-3, Caspase-9, and Bax. Molecular biological analysis showed that extracellular vesicles-encapsulated EGCG (EVs-EGCG) more significantly upregulated type II collagen expression by about 1.8-fold than EGCG alone, which was more beneficial for arthritis repair. Animal experiments revealed that these EGCG-coated extracellular vesicles significantly reduced swelling, decreased synovial hyperplasia, repaired cartilage, and attenuated arthritis-related pathology scores in arthritic rats. Measurement data showed that EVs-EGCG treatment reduced joint swelling by approximately 39.5% in rheumatoid rats. In vitro studies have shown that this EVs-EGCG can increase the expression of cartilage type II collagen and reduce apoptosis of chondrocytes. Moreover, it was demonstrated in vivo experiments to reduce cartilage destruction in rheumatoid arthritis rats, providing a solution for the treatment of rheumatoid arthritis.

scholarly journals T cell-derived extracellular vesicles are elevated in essential HTN

2020 ◽  
Vol 319 (5) ◽  
pp. F868-F875
Author(s):  
Sabrina La Salvia ◽  
Luca Musante ◽  
Joanne Lannigan ◽  
Joseph Christopher Gigliotti ◽  
Thu H. Le ◽  
...  
Keyword(s):  
Blood Pressure ◽  
T Cell ◽  
Extracellular Vesicles ◽  
Immune Cell ◽  
Kidney Tissue ◽  
Cell Communication ◽  
Organ Damage ◽  
In Vivo Model ◽  
Ang Ii

Extracellular vesicles (EVs) are novel mediators of cell-to-cell communication and appear to mediate the pathogenesis of hypertension (HTN). However, the mechanisms underlying the involvement of EVs in HTN remain unclear. The adaptive and innate immune systems play an important role affecting the kidney and vasculature in animal models of HTN. Evolving evidence shows that immune cell-derived EVs can modulate the immune system in a paracrine fashion and therefore may mediate the effects of inflammation in the pathogenesis of HTN. Therefore, we aimed to understand if specific subtypes of leukocyte/immune cell-derived EVs are altered in essential HTN using an in vivo model of angiotensin II (ANG II)-induced HTN. After 4 wk of ANG II treatment, EVs were isolated from the blood and kidney. EV origin and counts were characterized with Imaging Flow Cytometry, antibody panels targeting platelets, endothelial cells, and leukocytes including B and T cells, monocytes, and neutrophils. Leukocyte-derived EVs (CD45+) were elevated in the circulation and kidney tissue in ANG II-induced HTN. Subgroup analysis depicted T cell-derived EVs (CD3+) to be significantly elevated in ANG II-induced HTN (3.50 e+5 particles/mL) compared with control groups (9.16 e+4 particles/mL, P = 0.0106). T cell-derived EVs also significantly correlated with systolic blood pressure levels ( r2 = 0.898, P = 0.0012). In summary, leukocyte-derived EVs, and more specifically T cell-derived EVs (CD3+), are elevated in ANG II-induced HTN in the circulation and kidney tissue and correlate well with blood pressure severity. EVs from the circulation and kidney may be sensitive biomarkers for HTN and end-organ damage and may lead to new mechanistic insights in this silent disease.

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