PMID- 37554943 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230810 IS - 2189-7255 (Electronic) IS - 2189-7247 (Print) IS - 2189-7247 (Linking) VI - 9 IP - 3 DP - 2023 Aug TI - Effects of recombinant human soluble thrombomodulin on neutrophil extracellular traps in the kidney of a mouse model of endotoxin shock. PG - 225-230 LID - 10.20407/fmj.2022-026 [doi] AB - OBJECTIVES: Sepsis is a life-threatening condition characterized by multi-organ dysfunction due to host immune system dysregulation in response to an infection. During sepsis, neutrophils release neutrophil extracellular traps (NETs) as part of the innate immune response. However, excessive NETs play a critical role in the development of organ failure during sepsis. Although recombinant human soluble thrombomodulin (rTM) can inhibit NET formation in the lungs and liver of a mouse model of endotoxin shock, its effects on the kidneys are unclear. METHODS: The specific effects of NETs and rTM on the renal cortex and renal medulla were examined in a mouse model of endotoxin shock generated by intraperitoneal (i.p.) injection of lipopolysaccharide (LPS), followed by i.p. injection of rTM or an identical volume of saline 1 h later. RESULTS: LPS injection increased serum creatinine, blood urea nitrogen, and histone H3 levels. However, rTM administration significantly decreased histone H3 and citrullinated histone H3 (citH3) levels. Immunohistochemical analysis revealed no significant changes in citH3 quantity in the renal cortex of any group. However, in the renal medulla, the increase in citH3 induced by LPS was abolished in the LPS+rTM group. CONCLUSIONS: Our findings demonstrate that rTM can suppress NETs in the renal medulla of mice with endotoxin-induced acute kidney injury. FAU - Harada, Tatsuhiko AU - Harada T AD - Department of Anesthesiology and Critical Care Medicine, Fujita Health University, School of Medicine, Toyoake, Aichi, Japan. FAU - Shimomura, Yasuyo AU - Shimomura Y AD - Department of Anesthesiology and Critical Care Medicine, Fujita Health University, School of Medicine, Toyoake, Aichi, Japan. FAU - Nishida, Osamu AU - Nishida O AD - Department of Anesthesiology and Critical Care Medicine, Fujita Health University, School of Medicine, Toyoake, Aichi, Japan. FAU - Maeda, Munenori AU - Maeda M AD - Department of Anesthesiology and Critical Care Medicine, Fujita Health University, School of Medicine, Toyoake, Aichi, Japan. FAU - Kato, Yu AU - Kato Y AD - Department of Anesthesiology and Critical Care Medicine, Fujita Health University, School of Medicine, Toyoake, Aichi, Japan. FAU - Nakamura, Tomoyuki AU - Nakamura T AD - Department of Anesthesiology and Critical Care Medicine, Fujita Health University, School of Medicine, Toyoake, Aichi, Japan. FAU - Kuriyama, Naohide AU - Kuriyama N AD - Department of Anesthesiology and Critical Care Medicine, Fujita Health University, School of Medicine, Toyoake, Aichi, Japan. FAU - Komura, Hidefumi AU - Komura H AD - Department of Anesthesiology and Critical Care Medicine, Fujita Health University, School of Medicine, Toyoake, Aichi, Japan. LA - eng PT - Journal Article DEP - 20221227 PL - Japan TA - Fujita Med J JT - Fujita medical journal JID - 101745077 PMC - PMC10405902 OTO - NOTNLM OT - Kidney OT - Lipopolysaccharide OT - Neutrophil extracellular trap OT - Sepsis OT - Thrombomodulin EDAT- 2023/08/09 06:43 MHDA- 2023/08/09 06:44 PMCR- 2022/12/27 CRDT- 2023/08/09 04:07 PHST- 2022/06/07 00:00 [received] PHST- 2022/09/12 00:00 [accepted] PHST- 2023/08/09 06:44 [medline] PHST- 2023/08/09 06:43 [pubmed] PHST- 2023/08/09 04:07 [entrez] PHST- 2022/12/27 00:00 [pmc-release] AID - 10.20407/fmj.2022-026 [doi] PST - ppublish SO - Fujita Med J. 2023 Aug;9(3):225-230. doi: 10.20407/fmj.2022-026. Epub 2022 Dec 27.