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

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.

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

Health and Ecology Issues ◽

10.51523/2708-6011.2016-13-3-14 ◽

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.

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Faculty Opinions recommendation of Neutrophil extracellular traps induce endothelial dysfunction in systemic lupus erythematosus through the activation of matrix metalloproteinase-2.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718288683.793540036 ◽

2017 ◽

Author(s):

Cheng-Hock Toh

Keyword(s):

Systemic Lupus Erythematosus ◽

Endothelial Dysfunction ◽

Matrix Metalloproteinase ◽

Lupus Erythematosus ◽

Neutrophil Extracellular Traps ◽

Matrix Metalloproteinase 2 ◽

Systemic Lupus ◽

Extracellular Traps

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Faculty Opinions recommendation of Genetic variations in A20 DUB domain provide a genetic link to citrullination and neutrophil extracellular traps in systemic lupus erythematosus.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.736190778.793580563 ◽

2020 ◽

Author(s):

Frank DeLeo

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Neutrophil Extracellular Traps ◽

Genetic Variations ◽

Systemic Lupus ◽

Genetic Link ◽

Extracellular Traps

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

Scientific Reports ◽

10.1038/s41598-021-86390-0 ◽

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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FP098REDD1/AUTOPHAGY PATHWAY PROMOTES THROMBOINFLAMMATION AND FIBROSIS IN HUMAN SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) BY THE RELEASE OF NEUTROPHIL EXTRACELLULAR TRAPS (NETS)

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfy104.fp098 ◽

2018 ◽

Vol 33 (suppl_1) ◽

pp. i80-i80

Author(s):

Eleni Frangou ◽

Akrivi Chrysanthopoulou ◽

Konstantinos Kambas ◽

Alexandros Mitsios ◽

Stella Arelaki ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Neutrophil Extracellular Traps ◽

Human Systemic Lupus Erythematosus ◽

Systemic Lupus ◽

Extracellular Traps ◽

Autophagy Pathway

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Netosis in patients with systemic lupus erythematosus

Medical Immunology (Russia) ◽

10.15789/1563-0625-nip-1978 ◽

2020 ◽

Vol 22 (5) ◽

pp. 987-992

Author(s):

V. V. Zhelezko ◽

I. A. Novikova

Keyword(s):

Systemic Lupus Erythematosus ◽

Cell Cultures ◽

Lupus Erythematosus ◽

White Blood Cells ◽

Phagocytic Index ◽

Clinical Activity ◽

Systemic Lupus ◽

Complex Activity ◽

Extracellular Traps ◽

Functional Features

The article presents the data on assessment of functional features of neutrophils in 34 patients with systemic lupus erythematosus (SLE). Development of neutrophil extracellular traps (NETs) was evaluated in cell cultures incubated in vitro for 30 and 150 minutes (basal levels, NETBAS30 and NETBAS150, respectively), and in the presence of heat-inactivated S. аureus (strain ATCC 25923, 108 CFU/ml) (stimulated levels, NETST30 and NETST150, respectively). NET looks like thin free-lying extracellular fibrillar structures, 2-3 times exceeding the size of unchanged granulocyte. The result was expressed as percentage and relative amount of extracellular traps per 100 counted leukocytes. Phagocytic activity of neutrophils was evaluated as phagocytosis of S. аureus by counting the percentage of neutrophils that engulfed phagocytic index of microbial particles (PI); the average number of phagocytosed objects per neutrophil phagocytic number (PC). ROS-producing activity was determined in the reduction of Nitroblue Tetrazolium tested in spontaneous and stimulated S. аureus variants (NBTBAS and NBTST, respectively). The result was expressed as the percentage of formazan-positive cells per 100 white blood cells. Nitroxide-producing properties were determined using the Crow (1999) method in spontaneous and stimulated samples for the accumulation of the nitrated amino acid tyrosine (3-nitrothyrosine, 3-NTBAS, and 3-NTST, respectively). We revealed a decrease in ROS production, phagocytosis and NO-forming activity of neutrophils associated with increased netosis. Activation of the netosis was observed in cell cultures without stimulation, indicating the in vivo formation of networks in SLE. The NET increase is most pronounced in the patients with lupus nephritis (p < 0.05), and in remission of the disease (p < 0.05). We have revealed a correlation of NET formation parameters with duration and degree of SLE activity (rs = -0.6; p = 0.001, and rs = 0.39; p = 0.02, respectively); autoantibody titers (anti-dsDNA and ANA) (rs = 0.67; р = 0.047 and rs = 0.59; р = 0.034, respectively); prothrombin complex activity (rs = 0.6; p = 0.036), as well and urea and creatinine levels (rs = 0.47; p = 0.037 and rs = 0.39; p = 0.048, respectively). The parameters of NETs can be considered a promising biomarker for verifying the diagnosis of SLE, evaluation of clinical activity, disease severity, and predicting the development of complications.

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