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Enhanced Neutrophil Clearance by Low-Intensity Ultrasound with Neutrophil Extracellular Trap in Inflammed Synovium

Chung, Jee-In; Baik, Eun Joo
Department of Physiology, Ajou University School of Medicine
Neutrophil extracellular traps (NETs) in arthritic tissue are involved in the pathogenesis of arthritis; however, the functional role of NETs has not been clarified. Dead neutrophils are removed during resolution of inflammation. Delayed neutrophil clearance can lead to extended inflammation or even chronic autoimmune disease. Low-intensity ultrasound (LIUS) can be a feasible therapy for osteoarthritic joints. In this study, we investigated the effect of LIUS on synovial inflammation and its resolution. In CFA-induced synovitis, MPO-positive neutrophils exhibited a peak after 2-3 days, filling the inflammatory core. Monocytes and macrophages in the periphery later infiltrated the core, and were reduced thereafter. LIUS revealed reduced synovial hyperplasia and earlier MPO clearance. Neutrophils in the core of the inflamed synovium exhibited NET formation, which increased by LIUS. LIUS also induced NETs in peripheral polymorphonuclear cells in an intensity-dependent manner and potentiated phorbol myristate acetate (PMA)-induced NETosis. PMA-induced NETs were cleared by macrophages; the clearance was enhanced by LIUS. Taken together, NETs act in inflammatory synovitis, and LIUS enhanced the NETs and resulted in neutrophil clearance by enhancing the phagocytosis of macrophages. NETosis might be a factor for resolution of inflammation in arthritic synovium.
ACKNOWLEDGMENT: This study was supported by the Korea Science and Engineering Foundation through the Chronic Inflammatory Disease Research Center (NRF-2012R1A5A2051428) and a grant of the Korean Health Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Korea (A091120)
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