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- ItemNeutrophil extracellular trap formation is elicited in response to cold physical plasma(Hoboken, NJ : Wiley, 2016) Bekeschus, Sander; Winterbourn, VChristine C.; Kolata, Julia; Masur, Kai; Hasse, Sybille; Bröker, Barbara M.; Parker, Heather A.Cold physical plasma is an ionized gas with a multitude of components, including hydrogen peroxide and other reactive oxygen and nitrogen species. Recent studies suggest that exposure of wounds to cold plasma may accelerate healing. Upon wounding, neutrophils are the first line of defense against invading microorganisms but have also been identified to play a role in delayed healing. In this study, we examined how plasma treatment affects the functions of peripheral blood neutrophils. Plasma treatment induced oxidative stress, as assessed by the oxidation of intracellular fluorescent redox probes; reduced metabolic activity; but did not induce early apoptosis. Neutrophil oxidative burst was only modestly affected after plasma treatment, and the killing of Pseudomonas aeruginosa and Staphylococcus aureus was not significantly affected. Intriguingly, we found that plasma induced profound extracellular trap formation. This was inhibited by the presence of catalase during plasma treatment but was not replicated by adding an equivalent concentration of hydrogen peroxide. Plasma-induced neutrophil extracellular trap formation was not dependent on the activity of myeloperoxidase or NADPH oxidase 2 but seemed to involve short-lived molecules. The amount of DNA release and the time course after plasma treatment were similar to that with the common neutrophil extracellular trap inducer PMA. After neutrophil extracellular traps had formed, concentrations of IL-8 were also significantly increased in supernatants of plasma-treated neutrophils. Both neutrophil extracellular traps and IL-8 release may aid antimicrobial activity and spur inflammation at the wound site. Whether this aids or exacerbates wound healing needs to be tested.
- ItemPotentiating anti-tumor immunity with physical plasma(Amsterdam [u.a.] : Elsevier, 2018) Bekeschus, Sander; Clemen, Ramona; Metelmann, Hans-RobertThe age of checkpoint blockage emphasizes the importance of adaptive antitumor immune responses. This arm of immune defense is key in recognizing molecules via specific receptors to distinguish between self and foreign or mutated structures. Antigen-specific T-cells identify non-self epitopes, tumor-associated antigens, or neoepitopes on tumors to carry out attacks on malignant cells. Although tumor cells are immunogenic by nature, they have developed strategies to evade an immune response that would otherwise facilitate their clearance. Several steps in antitumor immunity utilize the toxic and signaling properties of reactive oxygen and nitrogen species (ROS/RNS). Cold physical plasmas are potent generators of such ROS/RNS and are demonstrated to have profound antitumor activity in vitro and in vivo. Here we discuss recent evidence and concepts on how plasmas may boost immunity against pathological cells. Specifically, plasma treatment may enhance the immunogenicity of tumor cells by induction of the immunogenic cancer cell death (ICD) and redox regulation of the antigen-presenting machinery. These aspects provide a rationale for localized plasma-based onco-therapies enhancing systemic antitumor immunity, which eventually may target distant tumor metastasis in cancer patients in a T-cell dependent fashion.