Neutrophil Extracellular Traps: A Walk on the Wild Side of Exercise Immunology
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REVIEW ARTICLE
Neutrophil Extracellular Traps: A Walk on the Wild Side of Exercise Immunology Thomas Beiter • Annunziata Fragasso Dominik Hartl • Andreas M. Nieß
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Ó Springer International Publishing Switzerland 2014
Abstract Intense exercise evokes a rapid and transient increase in circulating cell-free DNA (cf-DNA), a phenomenon that is commonly observed in a variety of acute and chronic inflammatory conditions. While the potential value of cf-DNA for the prediction of disease outcome and therapeutic response is well documented, the release mechanisms and biological relevance of cf-DNA have long remained enigmatic. The discovery of neutrophil extracellular traps (NETs) provided a novel mechanistic explanation for increased cfDNA levels. Now there is increasing evidence that NETs may contribute to cf-DNA in diverse infectious, non-infectious and autoinflammatory conditions, as well as in response to acute exercise. NETs have now been firmly established as a fundamental immune mechanism used by neutrophils to respond to infection and tissue injury. On the other side, aberrant formation of NETs appears to be a driving force in the pathogenesis of autoimmunity and cardiovascular disease. Thus, the emergence of NETs in the ‘exercising vasculature’ raises important questions considering beneficial effects, as well as occasional adverse effects, of exercise on immune homeostasis. This review gives an overview of the current state of research into the mechanisms of how NETs are released, contribute to host defence and participate in inflammatory disorders. We discuss the impact of exercise-induced NETs, considering a potentially beneficial role in the prevention of lifestyle-related diseases, as well as putative detrimental T. Beiter (&) A. Fragasso A. M. Nieß Department of Sports Medicine, Medical Clinic, Eberhard-KarlsUniversity of Tu¨bingen, Hoppe-Seyler-Str. 6, 72076 Tu¨bingen, Germany e-mail: [email protected] D. Hartl Department of Pediatrics I, Eberhard-Karls-University of Tu¨bingen, Tu¨bingen, Germany
effects that may arise in elite sports. Finally, we propose that exercise-induced cf-DNA responses could be exploited for diagnostic/prognostic purposes to identify individuals who are at increased risk of cardiovascular events or autoimmunity.
Key Points Intravascular neutrophil extracellular traps (NETs) contribute to transiently increased levels of circulating cell-free DNA (cf-DNA) in response to intense exercise. NETs participate in innate host defence by immobilizing, disarming and potentially killing microbial intruders, by preventing local and systemic spread of microorganisms and cellular debris, and by shaping adaptive immune responses. Aberrant release of NETs has been implicated in several pathological conditions, including autoimmune diseases, thrombosis, vascular inflammation and atherogenesis. In healthy individuals, exercise-triggered release of NETs is actively counterbalanced by a concomitant increase in serum deoxyribonuclease (DNase) activity. Aberrant or unresolved rel
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