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NETosis Induced by Serum of Patients with COVID-19 is Reduced with Reparixin or Antibodies Against DEK and IL-8.
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  • İrfan Kılıç,
  • Açelya Yaşar,
  • İrem Yalım Camcı,
  • Türkan Güzel,
  • Ayşegül Karahasan,
  • Tamer Yağcı,
  • Naci Çine,
  • Ayten Kandilci
İrfan Kılıç
Gebze Technical University
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Açelya Yaşar
Gebze Technical University
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İrem Yalım Camcı
Gebze Technical University
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Türkan Güzel
Gebze Technical University
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Ayşegül Karahasan
Marmara University Training and Research Hospital
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Tamer Yağcı
Gebze Technical University
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Naci Çine
Kocaeli University School of Medicine
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Ayten Kandilci
Gebze Technical University

Corresponding Author:[email protected]

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Abstract

DEK locates in the nucleus of the cells or the cytoplasmic granules of neutrophils and plays different roles in cellular processes including NETosis, a suicide mechanism of neutrophils. Here we showed that the interaction of rDEK with CXCR2 leads to NETosis, which could be reduced by the CXCR1/CXCR2 inhibitor reparixin. We found that IL-8, IL-6, IL1-β, MPO, and CitH3 were increased whereas DEK was decreased in the serum of COVID-19 patients. Interestingly, reparixin or anti-DEK antibody reduced the NETosis induced by the patients’ serum, suggesting that initial cytokine stimulation may further induce the release of DEK. Our results support the use of reparixin as a potential therapeutic strategy in COVID-19 and suggest that DEK-CXCR2 interaction plays a role in NETosis.