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Abstract
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Background. Intravascular neutrophil extracellular traps (NETs) releasing represents one of the mechanisms of immunothrombosis -- thrombi formation associated with immune reactions. NETs act as integrating link between immunity and hemostasis, thus acquiring particular importance in the sites of malignancy.
OBJECTIVES: to reveal whether the suicide NETosis can modify clotting parameters and the plasma level of essential immunoregulatory factors in vitro. Patients/Methods. The plasma concentration of interleukins (IL) -- IL-1β, IL-2, IL-4, IL-6, IL-10, free active transforming growth factor (TGF-β1), tumor necrosis factoralpha (TNF-α), interferon-γ (IFN-γ), chemokines CXCL8, CCL2, CXCL10 and I, II, III, IX, XI, XIII coagulation factors were measured before and after of experimental modeling of suicide NETosis in vitro. Coagulation process was assessed by thrombodynamics method. Cell culture of neutrophils and plasma were obtained from whole venous blood of 30 patients with newly diagnosed stage II-III colon cancer without metastases. The comparison group consisted of 40 healthy, age and gender matched volunteers. Plasma level of cytokines and clotting factors were measured by flow cytometry using multiplex assay panels.
RESULTS. Increasing of clotting rate by 5.5% and prolongation of lag-time were detected in both groups. There were no variations of coagulation factors level. The significant increase of plasma level of CXCL8, IL2 and free active TGF-β1 were detected in both groups in samples with netotic cells, when compared with their baseline concentration and with samples, contained resting cells.
CONCLUSIONS. Suicide NETosis is accompanied by acceleration of initial stage of fibrin clot formation through external way and by strong increase in CXCL8 concentration and less increase in IL-2 and TGF-β1 that can be considered as one of the ways how NETs contribute to hypercoagulation state and chronic inflammation development and also implement their tumorgenicity. © Parshina A.A., Tsybikov N.N., Tereshkov P.P., Karavaeva T.M., 2022
Language: ru |