Cytotoxicity of chromatin from macrophages in rhabdomyolysis-induced acute kidney injury

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K19497
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Kidney internal medicine
• Research Institution: Keio University
• Principal Investigator: Okubo Koshu 慶應義塾大学, 医学部(信濃町), 共同研究員 (60749125)
• Research Collaborator: KUROSAWA Miho ; URANO Yasuteru
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 横紋筋融解症 / 急性腎障害 / 白血球細胞外トラップ / Mac-1

Outline of Final Research Achievements

Rhabdomyolysis is a serious syndrome caused by skeletal muscle injury and the subsequent release of breakdown products from damaged muscle cells into systemic circulation. The muscle damage can lead to acute kidney injury (AKI).Recently, macrophages were implicated in the disease pathogenesis of rhabdomyolysis-induced AKI, but the precise molecular mechanism remains unclear. In the present study, we show that macrophages released extracellular traps (ETs) comprising DNA fibers and granule proteins in a mouse model of rhabdomyolysis. Heme-activated platelets released from necrotic muscle cells during rhabdomyolysis enhanced the production of macrophage extracellular traps (METs). Here we report, this unanticipated role for METs and platelets as a sensor of myoglobin-derived heme in rhabdomyolysis-induced AKI. Also, we found a new therapeutic tool for prevention of AKI after rhabdomyolysis, which might rescue some sufferers of this pathology.

Free Research Field

内科学、腎臓学、透析医学