scholarly journals THE ROLE OF PLATELETS IN FORMATION OF NEUTROPHIL EXTRACELLULAR TRAPS IN PATIENTS WITH IMMUNOCOMPLEX PATHOLOGY

2016 ◽  
pp. 66-70
Author(s):  
J. V. Zubkova ◽  
I. A. Novikova ◽  
V. V. Zhelezko
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Lupus Erythematosus ◽  
Rheumatoid Factor ◽  
Lupus Erythematosus ◽  
Neutrophil Extracellular Traps ◽  
In Vitro Cultures ◽  
Systemic Lupus ◽  
Extracellular Traps

The article presents the results of the assessment of the role of platelets in formation of extracellular traps by neutrophils. We have detected the ability of platelets to oppress the formation of extracellular traps by neutrophils in vitro cultures in patients with rheumatoid arthritis (RA) (n = 42) and systemic lupus erythematosus (SLE) (n = 24), but not in patients with hemorrhagic vasculitis (GW) (n = 15). The study has revealed the interrelation of NETosis and rheumatoid factor in patients with RA and SLE, as well as NET formation and number of platelets in patients with GW.

012 Proteomic analysis of neutrophil extracellular traps in rheumatoid arthritis and systemic lupus erythematosus

Rheumatology ◽  
2019 ◽  
Vol 58 (Supplement_3) ◽  
Author(s):  
Elinor A Chapman ◽  
Max Lyon ◽  
Deborah Simpson ◽  
David Mason ◽  
Robert J Beynon ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Proteomic Analysis ◽  
Neutrophil Extracellular Traps ◽  
Systemic Lupus ◽  
Extracellular Traps

scholarly journals NETs and oncologic process

2021 ◽  
Vol 15 (1) ◽  
pp. 107-116
Author(s):  
E. V. Slukhanchuk
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Neutrophil Extracellular Traps ◽  
Therapeutic Strategies ◽  
Innate Immune ◽  
Systemic Lupus ◽  
Extracellular Traps ◽  
Activated Neutrophils ◽  
Autoimmune Conditions

Neutrophil Extracellular Traps (NETs) represent the networks consisting of DNA, histones, and proteins produced by activated neutrophils. Such structures have been proved to play a crucial role in inducing neutrophil innate immune response in the pathogenesis of such autoimmune conditions as systemic lupus erythematosus, rheumatoid arthritis, psoriasis, as well as in the pathogenesis of other non-infectious processes, e. g., clotting disorders, thrombosis, diabetes, atherosclerosis, vasculitis and oncology diseases. Recent studies on animal models and human pathologies have uncovered a tremendous role for NETs in tumor progression and metastasis. In this regard, NETs should be considered as pro-oncogenic substances, which further investigation will provide an opportunity to develop new therapeutic strategies.

scholarly journals Role of Neutrophil Extracellular Traps Regarding Patients at Risk of Increased Disease Activity and Cardiovascular Comorbidity in Systemic Lupus Erythematosus

2019 ◽  
Vol 47 (11) ◽  
pp. 1652-1660 ◽  
Author(s):  
Stanley Moore ◽  
Hsin-Hsuan Juo ◽  
Christoffer T. Nielsen ◽  
Helena Tyden ◽  
Anders A. Bengtsson ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
At Risk ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Severe Disease ◽  
Neutrophil Extracellular Traps ◽  
Systemic Lupus ◽  
Extracellular Traps ◽  
Patients At Risk

ObjectiveNeutrophil extracellular traps (NET) are essential in host defense, but are also linked to inflammation and autoimmunity, including in systemic lupus erythematosus (SLE). We recently described that immune complexes (IC) induce NET formation, promoting SLE-like disease in mice. In the current study, we investigated, for the first time to our knowledge, the role of NET in human SLE and their association with disease activity and severity.MethodsLevels of NET (myeloperoxidase-DNA complexes) were analyzed in plasma from 4 cross-sectional SLE cohorts (n = 44–142), 1 longitudinal SLE cohort (n = 47), and healthy individuals (n = 100) using ELISA. Type I interferon activity was determined using a cell reporter system.ResultsPatients with SLE had elevated levels of NET in circulation compared to healthy controls (p < 0.01). NET levels identified patients with a severe disease phenotype characterized by IC-driven nephritis (p < 0.05). Though not associated with current disease activity (p = 0.20), levels of NET were associated with future increase in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) within 3 months (OR 1.75, p = 0.01), as well as an overall heightened SLEDAI over 1 year (p < 0.01). Finally, levels of NET were associated with arterial events (OR 5.0, p = 0.02) and endothelial cell activation (p < 0.001).ConclusionNET levels are elevated in patients with SLE, associated with IC-driven disease. NET levels provide significant clinical value in identifying patients at risk of active disease and/or severe disease, including nephritis and cardiovascular disease, and may allow for early interventions.

scholarly journals The role of peripheral immunological tolerance in the pathogenesis of systemic lupus erythematosus

2016 ◽  
Author(s):  
Αικατερίνη-Κυριακή Βλάχου
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Reactive Oxygen ◽  
Immunological Tolerance ◽  
Systemic Lupus ◽  
Extracellular Traps ◽  
Ifn Γ

Παρά την πολυπλοκότητα της αιτιοπαθογένειας των αυτοάνοσων νοσημάτων, της πλούσιας ποικιλίας των κλινικών συμπτωμάτων μεταξύ ασθενών και τη διαφορετική ανταπόκριση των ασθενών σε κοινές συμπτωματικές θεραπείες, υπάρχει μια κοινή αρχή: τα αυτοάνοσα νοσήματα αναπτύσσονται εξαιτίας της απώλειας της ανοσολογικής ανοχής στα αυτοαντιγόνα. Συνεπώς είναι αναγκαίο να διαλευκάνουμε τις γενεσιουργές αιτίες στις οποίες οφείλεται η αδυναμία ελέγχου και διατήρησης της ανοσολογικής ανοχής. Η κατανόηση των σχετικών υπεύθυνων μοριακών μηχανισμών θα προσφέρει την ευκαιρία ανάπτυξης στοχευμένων, έγκαιρων και αποτελεσματικότερων θεραπειών με κοινά οφέλη για ένα μεγάλο εύρος αυτοάνοσων νοσημάτων. Τα κατασταλτικά κύτταρα μυελικής προέλευσης (MDSCs) είναι ένα ετερογενής πληθυσμός μυελικών, ατελώς διαφοροποιημένων κυττάρων με ανοσορυθμιστικές ιδιότητες, τα οποία πρόσφατα έχουν συγκεντρώσει το ενδιαφέρον της επιστημονικής κοινότητας. Αποτελούνται από δύο υποπληθυσμούς κυττάρων, τα κοκκιοκυτταρικά (G-MDSCs) και τα μονοκυτταρικά (M-MDSCs). Το κύριο χαρακτηριστικό των MDSCs είναι ότι μπορούν να καταστείλουν τις ανοσολογικές αποκρίσεις των Τ λεμφοκυττάρων. Στην παρούσα ερευνητική εργασία, εστιάσαμε στο ρόλο των MDSCs στην παθογένεια του Συστηματικού Ερυθηματώδη Λύκου (ΣΕΛ). Ο ΣΕΛ είναι ένα συστεμικό αυτοάνοσο νόσημα, όπου η επιμένουσα απώλεια των ρυθμιστικών μηχανισμών διατήρησης της ανοσολογικής ανοχής συμβάλει στην παθογένεια της ασθένειας και την εγκαθίδρυση χρόνιας φλεγμονής. Για το λόγο αυτό, σχεδιάσαμε να εξετάσουμε το ρόλο των MDSC ρυθμιστικών κυττάρων στο ΣΕΛ, χρησιμοποιώντας το ζωικό μοντέλο NZB/W F1, ποντίκια τα οποία αυθόρμητα αναπτύσσουν ένα φαινότυπο παρόμοιο με του ΣΕΛ στον άνθρωπο. Με την εργασία αυτή δείχνουμε πως τα CD11bhighGr-1+ MDSCs ανιχνεύονται σε χαμηλά επίπεδα στα NZB/W F1 ποντίκια, τόσο στο υποκλινικό όσο και στο κλινικό στάδιο της νόσου. Αυτό κυρίως οφείλεται στη μειωμένη συχνότητα εμφάνισης των CD11bhighLy6G+ G-MDSCs στο μυελό των οστών και στα περιφερικά λεμφικά όργανα των ποντικιών με τη νόσο. Ο μειωμένος αριθμός των CD11bhighLy6G+ G-MDSC συνοδεύονται και από την ελαττωματική λειτουργία τους όσον αφορά στην in vitro καταστολή των CD4+ T λεμφοκυττάρων. Ενδιαφέρον προκαλεί ότι τα G-MDSC του λύκου όχι μόνο δεν μπορούν να καταστείλουν τα CD4+ T λεμφοκύτταρα, αλλά αντίθετα προκαλούν τον πολλαπλασιασμό κα την ενεργοποίηση τους. Σημαντικό είναι το εύρημα μας ότι τα CD11bhighLy6G+ G-MDSCs είναι μειωμένα στο λύκο εξαιτίας της αυξημένης απελευθέρωσης εξωκυττάριων παγίδων (Extracellular Traps, ETs) που προκαλείται από το φλεγμονώδες περιβάλλον του λύκου. Η αυξημένη απελευθέρωση των ETs (ΕTωση) εξαρτάται από την παραγωγή αντιδραστικών ριζών οξυγόνου (Reactive Oxygen Speces, ROS), η οποία επίσης προάγεται από τις φλεγμονώδεις ιδιότητες του περιβάλλοντος του λύκου. Τέλος, δείχνουμε ότι τρεις από τις εμπλουτισμένες κυτταροκίνες στο περιβάλλον του λύκου, οι IFN-α, IFN-γ και IL-6 έχουν την ικανότητα να επάγουν την ETωση στα κοκκιοκυτταρικά κύτταρα. Συμπερασματικά, τα δεδομένα μας αποδεικνύουν τη μειωμένη έκπτυξη των G-MDSC κυττάρων στο μικροπεριβάλλον του λύκου εξαιτίας του σχηματισμού των ETs, μια διαδικασία που αποτελεί ένα καινοφανή τύπο κυτταρικού θανάτου. Επιπλέον, παρέχουμε στοιχεία που υποστηρίζουν τη μεσολάβηση των ROS στο φαινόμενο αυτό. Η εξάλειψη των G-MDSC ενδεχομένως να έχει ως αποτέλεσμα την ελαττωματική ρύθμιση των ανοσολογικών αποκρίσεων συμβάλλοντας έτσι στην εξέλιξη της ασθένειας. Τα ευρήματά μας παρέχουν νέα στοιχεία στην κατανόηση της παθογένειας του ΣΕΛ και θα μπορούσε να συνεισφέρει στην ανάπτυξη νέων θεραπευτικών μεθόδων.

scholarly journals Effects of platelets on extracellular traps of neutrophils in patients with systemic lupus erythematosus

2021 ◽  
Vol 22 (6) ◽  
pp. 1173-1178
Author(s):  
I. A. Novikova ◽  
Z. V. Zubkova
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Functional Activity ◽  
Blood Platelets ◽  
White Blood Cells ◽  
Neutrophil Extracellular Traps ◽  
Systemic Lupus ◽  
Extracellular Traps ◽  
Activated Platelets

Platelets are central participants in hemostasis, and also contribute to the host inflammatory and immune responses. Platelets are known to have a direct effect on the formation of neutrophil extracellular traps. Moreover, the patients with systemic lupus erythematosus exhibit multidirectional disturbances in the functional activity of platelets and neutrophils. Changes in inflammatory and thrombotic events can be considered predictors for adverse clinical course in systemic pathology. The aim of present study was to evaluate the possible role of platelets in maintaining increased netosis in patients with systemic lupus erythematosus. Blood platelets and white blood cells from 29 patients with systemic lupus erythematosus (SLE) were subject to the study. We have registered the in vitro effects of platelets upon formation of extracellular traps by autologous neutrophils under the conditions of co-cultivation for 30 minutes (vital NETosis) and 150 minutes (suicidal NETosis), as well as the relationships between the platelet counts, their activity and the number of NETs observed. It was found that the severity and direction of the platelets effect upon NETosis in vitro cultures depends on the degree of activity of disease: in the 1st degree of SLE, the effect of platelets did not differ from healthy individuals, i.e., intact platelets suppress NETosis (p = 0.002), whereas ADP-induced patelets did not exert any effect); at the 2nd degree of activity, both intact and activated platelets increase NETotic activity (p = 0.03 and p = 0.04 for intact and activated platelets, respectively). In the patients with 3rd degree of the disease activity, platelets did not affect formation of NETs. Hyperactivation of platelets was detected in SLE patients, mostly pronounced in the cases with 2nd degree of activity. However, we have not revealed any significant relationships between the count of platelets, their functional activity (according to results of ADP-test aggregation), and the indexes of NETosis. At the same time, the counts of neutrophil extracellular traps in bloodstream depended on the concentration of C-reactive protein (r = 0.58; p = 0.02), the titer of autoantibodies (anti-SS-A and anti-SS-B) (r = 0.66; p = 0.04 and r = 0.76; p = 0.02, respectively), rheumatoid factor (r = 0.73; p = 0.007) and circulating immune complexes (r = 0.68; p = 0.02). The obtained results indicate that the platelet/neutrophil interactions are not the leading cause for increased NETs numbers in SLE, compared to significantly higher effects of soluble autoagressive factors.

scholarly journals The enrichment of neutrophil extracellular traps impair the placentas of systemic lupus erythematosus through accumulating decidual NK cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Meng Jiang ◽  
Nan Shen ◽  
Haibo Zhou ◽  
You Wang ◽  
Sihan Lin ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Nk Cells ◽  
Lupus Erythematosus ◽  
Neutrophil Extracellular Traps ◽  
Clinical Samples ◽  
Systemic Lupus ◽  
Extracellular Traps ◽  
Fetal Birth Weight ◽  
Immunological Disorder ◽  
Adverse Pregnancy

AbstractDespite the advances made in the management of pregnancies in women with systemic lupus erythematosus (SLE), the rate of adverse pregnancy outcomes is still higher than that in the general population. In the last few years, neutrophil extracellular traps (NETs) were proven to be detrimental in both autoimmune diseases and placental injury. We investigated whether NETs could be detected in the placentas of pregnant individuals with SLE and explored the relationship between NETs and decidual natural killer cells (dNKs), which comprise the majority of immune cells at the maternal–fetal interface, using clinical samples and animal models. In this study, we found that the infiltration of NETs and dNKs, especially CD56+CD16+ NK cells, was significantly increased in pregnant individuals with SLE with placental insufficiency. In the murine models of SLE, the number of dNKs was significantly decreased due to the decreased formation of NETs affected by Ly6G. Moreover, the histopathological placental injury was reduced, with a remarkable increase in fetal birth weight. This study shows that NETs may contribute to immunological disorder in the placenta and the pathological changes in pregnancies with SLE, which provides a research basis for further explorations of the mechanism of SLE in placental impairment.

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