INTRODUCTION: Neutrophil extracellular traps (NETs) are formed by activated neutrophils during the process of NETosis in which the nuclear material is released into extracellular space, including DNA molecules, citrullinated histones, and neutrophil granule enzymes, such as elastase. This material forms networks that are able not only to physically entrap bacteria but also to provide elevated concentration of bactericidal components. Over the last years, it has become clear that NETs can also be formed under numerous sterile inflammatory conditions, i.e., thrombosis, cancer, SLE, atherosclerosis, and diabetes. METHOD: We reviewed studies published until July 2016 to find possible associations between elevated cell-free DNA levels in dialyzed patients and the process of NETosis and its consequences. RESULTS: The process of NETosis, its elevated activation, or impaired clearance provides the link between clinical conditions and elevated levels of cell-free DNA found in plasma after the hemodialytic procedure which itself is able to activate neutrophils via platelets and ROS formation. NETs stimulate thrombosis and endothelial damage, and their formation may contribute to the development of spectrum of comorbidities described in dialyzed patients. CONCLUSION: The study of plasma cell-free DNA levels together with markers of NETosis could contribute to the evaluation of the influence of hemodialysis on the immune system of patients.

Department of Biology and Medical Genetics 1st Faculty of Medicine Charles University and General University Hospital Prague Albertov 4 128 00 Prague Czech Republic

Department of Nephrology 1st Faculty of Medicine Charles University and General University Hospital Prague U Nemocnice 2 128 08 Prague Czech Republic

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Cell-free DNA in plasma as an essential immune system regulator

Cell-free DNA from human plasma and serum differs in content of telomeric sequences and its ability to promote immune response