Resveratrol and tetrahydroisoquinoline effects on neutrophil sensitivity to NETosis formation in low‐risk essential thrombocythemia patients

• Published in: European journal of haematology Vol. 113; no. 1; pp. 44 - 53
• Main Authors: Shahriyary, Fahimeh, Amirzargar, Mohammad Reza, Vafajoo, Mahshid, Kooshari, Ahmad, Basi, Ali, Razavi, Seyed Mohsen, Gharegozlou, Behnaz, Shahidi, Minoo
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.07.2024
• Subjects: Adult; Aged; Carbon dioxide; Case-Control Studies; Cell death; Cytokines - metabolism; Disease Susceptibility; Enzyme-linked immunosorbent assay; essential thrombocythemia; Extracellular Traps - drug effects; Extracellular Traps - metabolism; Female; Flow cytometry; Fluorescence microscopy; Humans; Interleukin 8; Leukocytes (neutrophilic); Male; Microscopy; Middle Aged; NETosis; neutrophil extracellular traps; Neutrophils; Neutrophils - drug effects; Neutrophils - immunology; Neutrophils - metabolism; Plasma levels; Platelets; Resveratrol; Resveratrol - pharmacology; Resveratrol - therapeutic use; Tetrahydroisoquinoline; Tetrahydroisoquinolines - pharmacology; Tetrahydroisoquinolines - therapeutic use; Thrombocythemia, Essential - blood; Thrombocythemia, Essential - drug therapy; Thrombocythemia, Essential - metabolism; Thrombosis; Tumor necrosis factor-α; essential thrombocythemia; NETosis; neutrophil extracellular traps; resveratrol; Tetrahydroisoquinoline
• ISSN: 0902-4441; 1600-0609
• DOI: 10.1111/ejh.14196

Introduction Recent studies scrutinize how NETosis (a unique cell death mechanism of neutrophil), impacts thrombosis patients with essential thrombocythemia (ET). This research evaluates the susceptibility of ET neutrophils to form NETs and tests two potential inhibitors, resveratrol (RSV) and tetrahydroisoquinoline (THIQ), in vitro. Methods Platelet‐rich plasma from low‐risk ET patients was used, along with neutrophils from both patients and controls. NET formation assays, with or without RSV and THIQ treatment after LPS stimulation, were conducted in a CO2 incubator. Evaluation included flow cytometry and fluorescence microscopy for NET formation and ELISA for TNFα, IL8, and vWF:Ag levels in patient and control plasma. Results Neutrophils from ET patients released more NETs than controls, confirmed by flow cytometry and fluorescence microscopy. Additionally, patients had significantly higher plasma levels of IL8 and TNFα compared to controls, while RSV was more effective than THIQ in reducing NETosis rates in these patients. Conclusions In ET patients, a platelet counts over 1 million indicates the need for preventive treatment against thrombotic events. Similarly, in this study, RSV and THIQ significantly reduced the rate of NETosis in ET patients with higher platelet counts, and this role was more prominent in the case of the second inhibitor (RSV).