Murine scald models characterize the role of neutrophils and neutrophil extracellular traps in severe burns

Introduction Severe burns cause unique pathophysiological alterations especially on the immune system. As a basis for the understanding of immunological reactions in response to heat induced injury and to develop new surgical or pharmacological strategies, a murine scald model was optimized and biochemical aspects were analyzed, including the role of NETs and DNases. Methods The study included 30 C57BL/6 mice and 4 different scalds with varying exposure time to hot water. An additional scald group with a shorter observational time was generated to reduce mortality and study the very early phase of pathophysiology. At 24 h, respectively 72 h, blood was drawn and tissue (wound, liver, lung, spleen) was analyzed for markers of NETs, oxidative stress, apoptosis, bacterial translocation, and extracellular matrix organization. In addition, transcriptome analysis was performed from lung and liver tissue. Results Exposure to hot water for 7 s leads to significant systemic and local effects, however considerable late mortality. Therefore, in this groups, observational time was reduced to 24 h. To study later phases of burns (72 h) an exposure time of 6 s is beneficial. Both conditions lead to significant disorganization of collagen, increase in oxidative stress, NET markers (H3Cit, NE, MPO), apoptosis (cC3) and alternations in DNase 1 and 1l3 levels. Transcriptome analysis revealed remarkable alteration in genes involved in acute phase signaling, cell cohesion, extracellular matrix organization, and immune response. Conclusion Two different conditions of scald models were identified, serving for analysis of early (24 h) or late (72 h) effects of burns. Both models induced a reproducible and standardized scald injury. Characterization revealed important involvement of neutrophil activity and oxidative stress. Transcriptome analysis serves for mechanistic analysis of the involved pathways.