A role of NETs for damage of renal glomerular endothelial cells in ANCA-associated renal vasculitis

• Project/Area Number: 23591199
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Kyorin University
• Principal Investigator: KOMAGATA Yoshinori 杏林大学, 医学部, 准教授 (60281995)
• Co-Investigator(Kenkyū-buntansha): ARIMURA Yoshihiro 杏林大学, 医学部, 教授 (40222765)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 腎臓学 / ANCA関連血管炎 / 好中球 / 糸球体腎炎

Research Abstract

Pathological examination of renal biopsies from ANCA-associated vasculitis indicated that there was a glomerular infiltration of MPO-positive cells along with deposition of extracellular. Chromatin fibers called NETs are released from neutrophils. It has been known that NETs are implicated in the pathogenesis of ANCA-associated vasculitis (AAV). We observed NETs formation in order to investigate the role of NETs in AAV.
Peripheral blood neutrophils from AAV patients were primed with phorbolmyristate acetate(PMA) and the percentage of NETs producing cells were calculated. Neutrophils from active AAV patients produced much more fiber-like NETs than neutrophils from controls. The release of fiber-like NETs was markedly decreased by treatment for AAV. These data suggest the release of NETs by neutrophil at vascular endothelium is important for the pathogenesis of AAV.

Research Products

• [Journal Article] The role of myeloperoxidase and myeloperoxidase-antineutrophil cytoplasmic antibodies (MPO-ANCAs) in the pathogenesis of human MPO-ANCA-associated glomerulonephritis (2013)
  • Author(s): Arimura Y, Kawashima S, Yoshihara K, Komagata Y, Kaname S, Yamada A
  • Journal Title: Clin Exp Nephrol
  • Peer Reviewed
• [Journal Article] Immunopathologic co-localization of MPO, IgG, and C3 in glomeruli in human MPO-ANCA-associated glomerulonephritis (2013)
  • Author(s): Kawashima S、Arimura Y、Sano K、Kudo A、Komagata Y、Kaname S、Kawakami H、Yamada A
  • Journal Title: Clinical Nephrology Volume: 79-4 Pages: 292-301
  • Peer Reviewed
• [Journal Article] Immunopathologic co-localization of MPO, IgG, and C3 in glomeruli in human MPO-ANCA-associated glomerulonephritis. (2013)
  • Author(s): Kawashima S, Arimura Y, Sano K, Kudo A, Komagata Y, Kaname S, Kawakami H, Yamada A
  • Journal Title: Clin Nephrol. Volume: 79 Pages: 292-301
  • Peer Reviewed
• [Journal Article] The role of myeloperoxidase and myeloperoxidase-antineutrophil cytoplasmic antibodies(MPO-ANCAs) in the pathogenesis of human MPO-ANCA-associated glomerulonephritis. (2013)
  • Author(s): Arimura Y, Kawashima S,Yoshihara K,Komagata Y,Kaname S,Yamada A
  • Journal Title: Clin Exp Nephrol. Volume: 17 Issue: 5 Pages: 634-637
  • DOI: 10.1007/s10157-013-0787-7
  • Peer Reviewed
• [Journal Article] ANCA関連血管炎のANCA陰性再発 (2013)
  • Author(s): 駒形嘉紀、吉原堅、有村義宏
  • Journal Title: 日本臨床増刊号 血管炎 Volume: 71 Suppl 1 Pages: 612-616
• [Journal Article] Severity-based treatment for Japanese patients with MPO-ANCA-associated vasculitis : the JMAAV study (2012)
  • Author(s): Ozaki S, Atsumi T, Hayashi T, Ishizu A, Kobayashi S, Kumagai S, Kurihara Y, Kurokawa MS, Makino H, Nagafuchi H, Nakabayashi K, Nishimoto N, Suka M, Tomino Y, Yamada H, Yamagata K, Yoshida M, Yumura W, Amano K, Arimura Y, Hatta K, Ito S, Kikuchi H, Muso E, Nakashima H, Ohsone Y, Suzuki Y, Hashimoto H, Koyama A, Matsuo S, Kato H
  • Journal Title: Mod Rheumatol Volume: 22(3) Pages: 394-404
  • Peer Reviewed
• [Journal Article] Clinical findings on ANCA-associated renal vasculitis from the Japan RPGN registry obtained via a questionnaire survey (2012)
  • Author(s): Yamagata K, Usui J, Sugiyama H, Nitta K, Wada T, Muso E, Arimura Y, Koyama A, Makino H, Matsuo S
  • Journal Title: Clin Exp Nephrol
  • Peer Reviewed
• [Journal Article] Dual myeloperoxidase-antineutrophil cytoplasmic antibody-and antiglomerular basement membrane antibody-positive cases associated with prior pulmonary fibrosis : areport of four cases (2011)
  • Author(s): Nakabayashi K, Fujioka Y, Nagasawa T, Kimura T, Kojima K, Arimura Y, Yamada A
  • Journal Title: Clin Exp Nephrol Volume: 15 Pages: 226-234
  • Peer Reviewed
• [Journal Article] 多発血管炎性肉芽腫症(Wegener肉芽腫症)の肺病変 (2011)
  • Author(s): 駒形嘉紀、有村義宏
  • Journal Title: 呼吸器内科 Volume: 20 Pages: 402-409
• [Journal Article] ANCA関連血管炎に伴う尿細管間質性腎炎 (2011)
  • Author(s): 有村義宏
  • Journal Title: 日本腎臓学会誌 Volume: 53 Pages: 604-609
  • NAID: 10029737001
  • Peer Reviewed
• [Presentation] 好中球産生NETsのANCA関連血管炎の病態への関与 (2014)
  • Author(s): 村上華奈子、駒形嘉紀、森知真子、磯村杏耶、遠藤彰子、川嶋聡子、池谷紀子、要伸也、有村義宏、山田明
  • Organizer: 第58回日本リウマチ学会総会・学術集会
  • Place of Presentation: 東京
• [Presentation] A case of lung biopsy-proven MPO-ANCA positive granulomatosis with polyangiitis (2013)
  • Author(s): Murakami K, Saito M, Komagata Y, Yoshihara K, Kaname S, Arimura Y, Yamada A, Nakamoto Y, Ishida M, Hikgaki M, Takizawa H, Kawauchi R, Goya T, Fujiwara M, Yazawa T, Kamma H
  • Organizer: 16th International Vasculitis & ANCA Workshop
  • Place of Presentation: France
• [Presentation] Autoantibodies for several antigens in neutrophil cytoplasm other than PR3 and MPO also promote release of NETs from neutrophils. (2013)
  • Author(s): Y. Komagata, S. Amonpatumrat, K. Sano, S. Kawashima, S. Kaname, Y. Arimura, A. Yamada
  • Organizer: 16th International Vasculitis & ANCA Workshop
  • Place of Presentation: Paris, France
• [Presentation] Autoantibodies for several antigens in neutrophil cytoplasm other than PR3 and MPO also promote release of NETs from neutrophils. (2013)
  • Author(s): Komagata Y, Amonpatumrat S, Sano K, Kawashima S, Kaname S, Arimura Y, Yamada A
  • Organizer: 16th International Vasculitis & ANCA Workshop
  • Place of Presentation: Paris
• [Presentation] MPO陽性細胞浸潤、糸球体毛細血管へのMPO沈着は糸球体壊死と関連する (2012)
  • Author(s): 川嶋聡子、有村義宏、横井陽子、窪田沙也加、吉原堅、駒形嘉紀、要伸也、山田明
  • Organizer: 第55回日本腎臓学会学術総会
  • Place of Presentation: 横浜
• [Presentation] ANCA-negative Relapse of AAV: A 79-year-old Female with Fever and Proteinuria (2012)
  • Author(s): Yoshinori Komagata
  • Organizer: The Asia Pacific Meeting of Vasculitis and ANCA Workshop 2012(招待講演)
  • Place of Presentation: Tokyo Conference Center Shinagawa
• [Presentation] Differencein clinical feature between MPO-and PR3-ANCA-positive Wegener's granulomatosis (2011)
  • Author(s): Komagata Y, Nomura K, Kawashima S, Yoshihara K, Kaname S, Arimura Y, Yamada A
  • Organizer: 15TH INTERNATIONAL VASCULITIS&ANCA WORKSHOP
  • Place of Presentation: NORTH CAROLINA、USA
• [Presentation] In situ-immune complex(MPO-anti MPO antibody)relates to glomerular capillary in human-MPO-ANCA associated glomerulonephritis (2011)
  • Author(s): Kawashima S、Komagata Y、Arimura Y、Yamada A
  • Organizer: 15TH INTERNATIONAL VASCULITIS&ANCA WORKSHOP
  • Place of Presentation: NORTH CAROLINA、USA
• [Presentation] MPO-ANCA関連腎炎における糸球体毛細血管傷害の病理組織学的検討一MPO・免疫グロブリンの関与一 (2011)
  • Author(s): 川嶋聡子、福岡利仁、吉原堅、駒形嘉紀、要伸也、有村義宏、山田明
  • Organizer: 第54回日本腎臓学会学術集会
  • Place of Presentation: 横浜
• [Presentation] Wegener肉芽腫症におけるMPO-ANCA陽性患者とPR3-ANCA陽性患者との臨床像の相違 (2011)
  • Author(s): 駒形嘉紀、有村義宏、野村和史、齋藤督芸、川嶋聡子、池谷紀子、小路仁、福岡利仁、軽部美穂、吉原堅、要伸也、中林公正、山田明
  • Organizer: 第55回日本リウマチ学会総会・学術集会
  • Place of Presentation: 神戸