Studies on the neutrophil-mediated transport of Shiga toxins

• Project/Area Number: 20591293
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: National Research Institute for Child Health and Development
• Principal Investigator: TSUNAWAKI Shohko National Research Institute for Child Health and Development, 研究所・母児感染研究部, 室長 (00211384)
• Co-Investigator(Kenkyū-buntansha): 守屋 美恵 独立行政法人国立成育医療研究センター, 母児感染研究部, 共同研究員 (60470001) ; 塩田 清二 昭和大学, 医学部, 教授 (80102375)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 好中球 / 志賀毒素 / スフィンゴ糖脂質 / 溶血性尿毒症 / ラクトシルセラミド / スフィゴ糖脂質 / 細菌 / 溶血尿毒素 / 溶血尿毒症

Research Abstract

Enterohemorrhagic Escherichia coli (EHEC), a major pathogen of pediatric hemorrhagic colitis, cause hemolytic uremic syndrome (HUS) and encephalopathy. Shiga toxins (Stx1 and Stx2) produced by EHEC damage target cells which highly express Gb3, but the transport mechanism of Stxs from the intestinal tract to the target cells is unclear. In this study, we demonstrate that Stxs bind to LacCer in neutrophils and accumulate in the nucleus bypassing lysosomes and Golgi bodies. In view of neutrophil accumulation in glomeruli of patients with HUS, they should transport Stxs to target cells from the intestinal tract.

Research Products

• [Journal Article] Monocarboxylate transporter-1 is required for cell death in mouse chondrocytic ATDC5 cells exposed to interleukin-1b via late-phase activation of nuclear factor кB and expression of phagocyte-type NADPH-oxidase. (2011)
  • Author(s): Yoshimura K, Miyamoto Y, Yasuhara R, Maruyama T, Akiyama T, Yamada A, Takami M, Suzawa T, Tsunawaki S, Tachikawa T, Baba K, Kamijo R.
  • Journal Title: J Biol Chem. 286 Pages: 14744-14752
• [Journal Article] Monocarboxylate transporter-1 is required for cell death in mouse chondrocytic ATDC5 cells exposed to interleukin-l β via late-phase activation of nuclear factor κB and expression of phagocyte-type NADPH-oxidase (2011)
  • Author(s): Yoshimura K
  • Journal Title: J Biological Chemistry
  • Peer Reviewed
• [Journal Article] Gp91^<phox>(NOX2) in classically activated microglia exacerbates traumatic brain injury. (2010)
  • Author(s): Dohi K, Ohtaki H, Nakamachi T, Yofu S, Satoh K, Miyamoto K, Song D, Tsunawaki S, Shioda S, Aruga T.
  • Journal Title: J Neuroinflammation. 7 Pages: 41-51
• [Journal Article] Gp91 phox (NOX2) in classically activated microglia exacerbates traumatic brain injury (2010)
  • Author(s): Dohi K
  • Journal Title: J Neuroinflammation Volume: 7 Pages: 41-51
  • Peer Reviewed
• [Journal Article] (2009)
  • Author(s): 綱脇祥子
  • Journal Title: 臨床検査ガイド(2009〜2010)(文光堂) Pages: 593-598
• [Journal Article] Expression of NADPH oxidases and enhanced H2O2-generating activity in human coronary artery endothelial cells upon induction with tumor necrosis factor-α. (2008)
  • Author(s): Yoshida LS, Tsunawaki S.
  • Journal Title: Int.Immunopharmacol. 8 Pages: 1377-1385
• [Journal Article] Expression of NADPH oxidases and enhanced H_2O_2-generating activity in human coronary artery endothelial cells upon induction with tumor necrosis factor-α (2008)
  • Author(s): Lucia S. Yoshida
  • Journal Title: International Immunopharmacology 8 Pages: 1377-1385
  • Peer Reviewed
• [Presentation] Dynamic analysis of the Nox family NADPH oxidases in the pathogenesis of Kawasaki disease. (2009)
  • Author(s): 綱脇祥子、内田友祐、吉田ルシア幸子、守屋美恵.
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
• [Presentation] Is the neutrophil NADPH oxidase (Nox2) involved in the pathogenesis of Kawasaki disease? (2009)
  • Author(s): 守屋美恵、吉田ルシア幸子、綱脇祥子.
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] Expression of Nox family NADPH oxidases and enhanced ROS-generating activity in human coronary artery endothelial cells upon induction with tumor necrosis factor-α. (2008)
  • Author(s): 綱脇祥子, 吉田ルシア幸子
  • Organizer: Gordon Research Conference (meeting for Nox family NADPH oxidases)
  • Place of Presentation: New London, New Hampshire, USA
• [Book] 臨床検査ガイド (2010)
  • Author(s): 綱脇祥子
  • Total Pages: 6
  • Publisher: 文光堂
• [Book] 白血球機能検査2009-2010.(臨床検査ガイド「Medical Practice編集委員会編」)(2009) (2009)
  • Author(s): 綱脇祥子
  • Publisher: 文光堂
• [Remarks]
  • URL: http://www.ncchd.go.jp
• [Remarks]
  • URL: http://www.ncchd.go.jp/
• [Remarks]
  • URL: http://www.ncchd.go.jp/