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Intravascular neutrophil extracellular traps capture bacteria from the bloodstream during sepsis

McDonald, B;Urrutia, R;Yipp, BG;Jenne, CN;Kubes, P;

During the systemic inflammatory response of severe sepsis, neutrophils accumulate in the liver microcirculation, but their functional significance is largely unknown. We show that neutrophils migrate to liver sinusoids during endotoxemia and sepsis where they exert protective effects by releasing neutrophil extracellular traps (NETs), which are DNA-based structures that capture and eliminate microbes. NETs released into the vasculature ensnare bacteria from the bloodstream and prevent dissemination. NET production requires platelet-neutrophil interactions and can be inhibited by platelet depletion or disruption of integrin-mediated platelet-neutrophil binding. During sepsis, NET release increases bacterial trapping by 4-fold (beyond the basal level provided by resident intravascular macrophages). Blocking NET formation reduces the capture of circulating bacteria during sepsis, resulting in increased dissemination to distant organs. Thus, NETs ensnare circulating bacteria and provide intravascular immunity that protects against bacterial dissemination during septic infections.