• Takayoshi Gocho, Hisatake Mori, Md Monirul Islam, Yuki Maruchi, Nobuyoshi Takenaka, Atsutoshi Tomino, Masanobu Tsuda, Hideki Kano, and Naoshi Takeyama.
• Department of Emergency and Critical Care Medicine, Aichi Medical University, Aichi, Japan.
• Shock. 2020 Jul 1; 54 (1): 44-49.

AbstractComponents of neutrophil extracellular traps (NETs) are released into the circulation by neutrophils and contribute to microcirculatory disturbance in sepsis. Removing NET components (DNA, histones, and proteases) from the circulation could be a new strategy for counteracting NET-dependent tissue damage. We evaluated the effect of hemoperfusion with a polymyxin B (PMX) cartridge, which was originally developed for treating gram-negative infection, on circulating NET components in patients with septic shock, as well as the effect on phorbol myristate acetate (PMA)-stimulated neutrophils obtained from healthy volunteers. Ex vivo closed loop hemoperfusion was performed through PMX filters in a laboratory circuit. Whole blood from healthy volunteers (incubated with or without PMA) or from septic shock patients was perfused through the circuit. For in vivo experiment blood samples were collected before and immediately after hemoperfusion with PMX to measure the plasma levels of cell-free NETs. The level of cell-free NETs was assessed by measuring myeloperoxidase-associated DNA (MPO-DNA), neutrophil elastase-associated DNA (NE-DNA), and cell-free DNA (cf-DNA). Plasma levels of MPO-DNA, NE-DNA, and cf-DNA were significantly increased after 2 h of PMA stimulation. When the circuit was perfused with blood from septic shock patients or PMA-stimulated neutrophils from healthy volunteers, circulating levels of MPO-DNA, NE-DNA, and cf-DNA were significantly reduced after 1 and 2 h of perfusion with a PMX filter compared with perfusion without a PMX filter. In 10 patients with sepsis, direct hemoperfusion through filters with immobilized PMX significantly reduced plasma levels of MPO-DNA and NE-DNA. These ex vivo and in vivo findings demonstrated that hemoperfusion with PMX removes circulating NET components. Selective removal of circulating NET components from the blood could be effective for prevention/treatment of NET-related inappropriate inflammation and thrombogenesis in patients with sepsis.

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