TY - JOUR T1 - Neutrophils delay repair process in Wallerian degeneration by releasing NETs outside the parenchyma JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.202201399 VL - 5 IS - 10 SP - e202201399 AU - Yasuhiro Yamamoto AU - Ken Kadoya AU - Mohamad Alaa Terkawi AU - Takeshi Endo AU - Kohtarou Konno AU - Masahiko Watanabe AU - Satoshi Ichihara AU - Akira Hara AU - Kazuo Kaneko AU - Norimasa Iwasaki AU - Muneaki Ishijima Y1 - 2022/10/01 UR - https://www.life-science-alliance.org/content/5/10/e202201399.abstract N2 - Although inflammation is indispensable for the repair process in Wallerian degeneration (WD), the role of neutrophils in the WD repair process remains unclear. After peripheral nerve injury, neutrophils accumulate at the epineurium but not the parenchyma in the WD region because of the blood–nerve barrier. An increase or decrease in the number of neutrophils delayed or promoted macrophage infiltration from the epineurium into the parenchyma and the repair process in WD. Abundant neutrophil extracellular traps (NETs) were formed around neutrophils, and its inhibition dramatically increased macrophage infiltration into the parenchyma. Furthermore, inhibition of either MIF or its receptor, CXCR4, in neutrophils decreased NET formation, resulting in enhanced macrophage infiltration into the parenchyma. Moreover, inhibiting MIF for just 2 h after peripheral nerve injury promoted the repair process. These findings indicate that neutrophils delay the repair process in WD from outside the parenchyma by inhibiting macrophage infiltration via NET formation and that neutrophils, NETs, MIF, and CXCR4 are therapeutic targets for peripheral nerve regeneration. ER -