Challenging study to clarify mechanisms of multiple organ failure

• Project/Area Number: 24659802
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Emergency medicine
• Research Institution: Juntendo University
• Principal Investigator: TANAKA Hiroshi 順天堂大学, 医学(系)研究科(研究院), 教授 (90252676)
• Co-Investigator(Kenkyū-buntansha): INOUE Yoshiaki 順天堂大学, 医学部, 先任准教授 (60379196) ; SUMI Yuka 順天堂大学, 医学部, 准教授 (40403084) ; SUGINAKA Hiroshi 順天堂大学, 医学部, 助手 (30510424) ; MORIKAWA Miki 順天堂大学, 医学部, 助手 (40621892) ; ISHIKAWA Kohei 順天堂大学, 医学部, 助手 (50621900) ; IWABUCHI Kazuhisa 順天堂大学, 医療看護学部, 教授 (10184897) ; ARAKI Yoshihiko 順天堂大学, 大学院, 准教授 (70250933)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 多臓器不全 / 敗血症 / DAMPｓ / ATP / 白血球機能 / 蛍光イメージング / 心肺停止蘇生後 / DIC / DAMPs

Research Abstract

ATP is involved in both intra and extracellular signaling. Neutrophils (PMNs) have a pivotal role in inflammation response. In sepsis patients, plasma ATP levels and CD11b were significantly higher than healthy controls, and the CD11b correlates with plasma ATP. These data suggest that ATP release from damaged cells or activated inflammatory cells stimulates PMNs via ATP receptors and triggers inflammation in sepsis. Sepsis-induced DIC is associated with a high mortality rate. The function and deformability of PMN change in patients with sepsis induced DIC was evaluated. We clarified that PMN deformability and activation correlated with the severity of sepsis-induced DIC. Fluorescence imaging of ATP in human PMNs with chemosensors (PMAP-1, MitoAP-1) was established. This method would contribute to understanding the dynamics of ATP in PMNs and elucidating their diverse physiological functions in inflammation.

Research Products

• [Journal Article] Pseudomonas-derived ceramidase induces production of inflammatory mediators from human keratinocytes via sphingosine-1-phosphate (2014)
  • Author(s): Oizumi A, Nakayama H, Okino N, Iwahara C, Kina K, Matsumoto R, Ogawa H, Takamori K, Ito M, Suga Y, Iwabuchi K
  • Journal Title: PLos One Volume: 25 Pages: 89402-89402
  • Peer Reviewed
• [Journal Article] Leukocyte deformability is a novel biomarker to reflect sepsis-induced disseminated intravascular coagulation (2014)
  • Author(s): Morikawa M, Inoue Y, Sumi Y, Kuroda Y, Tanaka H
  • Journal Title: Acute Medicine & Surgery Volume: (in print)
  • Peer Reviewed
• [Journal Article] Plasma ATP is required for neutrophil activation in a mouse sepsis model (2014)
  • Author(s): Sumi Y, Woehrle T, Chen Y, Bao Y, Li X, Yao Y, Inoue Y, Tanaka H, Junger WG
  • Journal Title: Shock Volume: (in print)
  • Peer Reviewed
• [Journal Article] Leukocyte deformability is a novel biomarker to reflect sepsis-induced disseminated intravascular coagulation. (2014)
  • Author(s): Morikawa M, Inoue Y, Sumi Y, Kuroda Y, Tanaka H
  • Journal Title: Acute Medicine & Surgery Volume: 1
  • Peer Reviewed
• [Journal Article] Plasma ATP is required for neutrophil activation in a mouse sepsis model. (2014)
  • Author(s): Sumi Y, Woehrle T, Chen Y, Bao Y, Li X, Yao Y, Inoue Y, Tanaka H, Junger WG.
  • Journal Title: Shock Volume: -
  • Peer Reviewed
• [Journal Article] Pseudomonas-derived ceramidase induces production of inflammatory mediators from human keratinocytes via sphingosine-1-phosphate. (2014)
  • Author(s): Oizumi A, Nakayama H, Okino N, Iwahara C, Kina K, Matsumoto R, Ogawa H, Takamori K, Ito M, Suga Y, Iwabuchi K.
  • Journal Title: PLoS One Volume: 25
  • Peer Reviewed
• [Journal Article] Recombinant human soluble thrombomodulin in sepsis-induce disseminated intravascular coagulation : a multicenter propensity score analysis (2013)
  • Author(s): Yamakawa K, Ogura H, Fujimi S, Morikawa M, Ogawa Y, Mohri T, Nakamori Y, Inoue Y, Kuwagata Y, Tanaka H, Hamasaki T, Shimazu T
  • Journal Title: Intensive Care Med Volume: 39 Pages: 644-652
  • Peer Reviewed
• [Journal Article] Whole body CT検査を行った敗血症5例 (2013)
  • Author(s): 柳川洋一、小原圭一朗、平野洋平、中村有紀、松田繁、相原恒一郎、渡邉心、内藤俊夫、射場敏明、田中裕
  • Journal Title: 日臨救急医会誌 Volume: 16 Pages: 40-43
  • Peer Reviewed
• [Journal Article] Sevoflurane suppresses tumour necrosis factor-α-induced inflammatory responses in small airway epithelial cells after anoxia/reoxygenation. (2013)
  • Author(s): Watanabe K, Iwahara C, Nakayama H, Iwabuchi K, Matsukawa T, Yokoyama K, Yamaguchi K, Kamiyama Y, Inada E.
  • Journal Title: Br J Anaesth Volume: 110 Issue: 4 Pages: 637-645
  • DOI: 10.1093/bja/aes469
  • Peer Reviewed
• [Journal Article] Recombinant human soluble thrombomodulin in sepsis-induced disseminated intravascular coagulation: a multicenter propensity score analysis. (2013)
  • Author(s): Yamakawa K, Ogura H, Fujimi S, Morikawa M, Ogawa Y, Mohri T, Nakamori Y, Inoue Y, Kuwagata Y, Tanaka H, Hamasaki T, Shimazu T
  • Journal Title: Intensive Care Med Volume: 39 Issue: 4 Pages: 644-652
  • DOI: 10.1007/s00134-013-2822-2
  • Peer Reviewed
• [Journal Article] 臓器機能障害のメカニズムとしてのミトコンドリア機能不全 (2012)
  • Author(s): 角由佳
  • Journal Title: 救急・集中治療 Volume: 24 Pages: 1068-1075
• [Journal Article] Membran microdomains in immunity-Glycosphingolipid-enri hed domain mediated innate immune responses- (2012)
  • Author(s): Iwabuchi K, Nakayama H, Sasuda H, Kina K, Ogawa H, Takamori K
  • Journal Title: Biofactors Volume: 38 Pages: 275-283
  • Peer Reviewed
• [Journal Article] Membrane microdomains in immunity - Glycosphingolipid-enriched domain mediated innate immune responses- (2012)
  • Author(s): Iwaabuchi K, Nakayama H, Sasuda H, Kina K, Ogawa H, Takamori K
  • Journal Title: Biofactors Volume: 38 Pages: 275-283
  • Peer Reviewed
• [Presentation] Fluorescence Imaging of ATP in Human Neutrophils with Organelle-Localizable Fluorescent Chemosensors (2014)
  • Author(s): Sueyoshi K, Sumi Y, Inoue Y, Kuroda K, Ishii K, Tanaka H
  • Organizer: The 43rd Critical Care Congress
  • Place of Presentation: San-Francisco, USA
• [Presentation] 救急領域におけるAcinetobacter Baumannii感染のリスクファクターについて (2014)
  • Author(s): 井上貴昭、角由佳、岡本健、佐々木信一、田中裕
  • Organizer: 第41回日本集中治療医学会
  • Place of Presentation: 岡山
• [Presentation] Fluroescence imaging of ATP in human neutrophils with organelle-localizable fluorescent chemosensors. (2014)
  • Author(s): Sueyoshi K, Sumi Y, Inoue Y, Kuroda K, Ishii K, Nakayama H, Iwabuchi K, Kurishita Y, Hamachi I, Tanaka H.
  • Organizer: 第43回 Society of Critical Care Medicine.
  • Place of Presentation: サンフランシスコ
• [Presentation] 外傷患者に対する生体侵襲評価のための新たなbiomarkerの開発 (2013)
  • Author(s): 井上貴昭, 福本祐一, 石川浩平, 杉中宏司, 末吉孝一郎, 西山和孝, 角由佳, 竹内悠二, 林伸洋, 大出靖将, 岡本健, 田中裕
  • Organizer: 第回日本外傷学会
  • Place of Presentation: 久留米
• [Presentation] Plasma ATP levels and outcome of sepsis (2013)
  • Author(s): Sumi Y, Inoue Y, Junger WG, Okamoto K, Tanaka H
  • Organizer: The 36th Annual Conference on Shock
  • Place of Presentation: San Diego, USA
• [Presentation] 白血球変形能の測定と敗血症DICの診断 (2013)
  • Author(s): 森川美樹,, 井上貴昭, 角由佳, 福本祐一, 平野洋平, 西山和孝, 末吉孝一郎, 松田繁, 岡本健, 田中裕
  • Organizer: 第16回日本臨床救急医学会
  • Place of Presentation: 東京
• [Presentation] ATP/アデノシンバランスからみた敗血症 (2013)
  • Author(s): 角由佳、井上貴昭、Junger WG, 田中裕
  • Organizer: 第41回日本救急医学会
  • Place of Presentation: 東京
• [Presentation] 心肺停止蘇生後の全脳虚血再灌流障害における酸化能と抗酸化能、およびATPと神経学的予後との相関 (2013)
  • Author(s): 石川浩平、井上貴昭, 角由佳, 田中裕
  • Organizer: 第41回日本救急医学会
  • Place of Presentation: 東京
• [Presentation] Clinical risk factors of Acinetobacter Baumannii in ICU patients (2013)
  • Author(s): Inoue Y, Sumi Y, Okamoto K, Sasaki S, Tanaka H
  • Organizer: The 7th Asian Conference on Emergency Medicine
  • Place of Presentation: Tokyo
• [Presentation] Plasma ATP in SIRS patients (2013)
  • Author(s): Sumi Y, Sueyoshi K, Inoue Y, Tanaka H, Linglin Lee
  • Organizer: The 7th Asian Conference on Emergency Medicine
  • Place of Presentation: Tokyo
• [Presentation] Plasma ATP in SIRS patients. (2013)
  • Author(s): 角由佳、末吉孝一郎、井上貴昭、田中裕、Linglin Lee、Junger Wolfgang G
  • Organizer: 第7回Asian Conference in Emergency Medicine
  • Place of Presentation: 東京
• [Presentation] 心肺停止蘇生後の全脳虚血再灌流障害における酸素化能と抗酸化能、及びATPと神経学的予後との相関 (2013)
  • Author(s): 石川浩平、西山和孝、井上貴昭、角由佳、田中裕
  • Organizer: 第41回日本救急医学会総会
  • Place of Presentation: 東京
• [Presentation] 胃電図検査を用いた生体侵襲患者における胃機能評価の試み (2013)
  • Author(s): 平野洋平、西山和孝、石川浩平、森川美樹、杉中宏司、末吉孝一郎、吉原智之、角由佳、井上貴昭、松田繁、田中裕
  • Organizer: 第41回日本救急医学会総会
  • Place of Presentation: 東京
• [Presentation] 敗血症・重症感染症の生存率向上に向けた研究と取り組み：ATP/アデノシンバランスからみた敗血症 (2013)
  • Author(s): 角由佳、吉原智之、末吉孝一郎、井上貴昭、松田繁、岡本健、田中裕、Junger WG
  • Organizer: 第41回日本救急医学会総会
  • Place of Presentation: 東京
• [Presentation] 白血球変形能の測定と敗血症性DICの診断 (2013)
  • Author(s): 森川美樹、井上貴昭、角由佳、田中裕
  • Organizer: 第16回日本臨床救急医学会総会
  • Place of Presentation: 東京
• [Presentation] Plasma ATP levels and outcome of sepsis. (2013)
  • Author(s): Sumi Y, Inoue Y, Junger WG, Okamoto K, Tanaka H, Lee L
  • Organizer: 第36回 Annual Conference on Shock
  • Place of Presentation: サンデイエゴ
• [Presentation] 心肺停止後における全脳虚血再還流障害に伴う酸化ストレスと抗酸化能の変化について (2012)
  • Author(s): 石川浩平、井上貴昭、森川美樹、角由佳、岡本健、田中裕
  • Organizer: 第25回日本脳死脳蘇生学会
  • Place of Presentation: 宮崎
• [Presentation] 熱傷重症度のinnovation：生体ストレス・好中球機能をbiomarkerとする熱傷重症度の評価 (2012)
  • Author(s): 井上貴昭、角由佳、岡本健、田中裕
  • Organizer: 第38回日本熱傷学会
  • Place of Presentation: 東京
• [Presentation] Plasma ATP levels and neutrophil activation in sepsis (2012)
  • Author(s): Sumi Y, Morikawa M, Inoue Y, Matsuda S, Okamoto K, Tanaka H, Li L, Kuroda Y, Junger WG
  • Organizer: The 35th Annual Conference on Shock
  • Place of Presentation: Miami Beach, Florida
• [Presentation] 血漿中ATPを経時的に測定した重症急性膵炎の1例 (2012)
  • Author(s): 角由佳、黒田洋子、森川美樹、井上貴昭、松田繁、岡本健、Wolfgang Junger、田中裕
  • Organizer: 第33回日本炎症・再生医学会
  • Place of Presentation: 福岡
• [Presentation] 心肺停止蘇生後の虚血再灌流障害における酸化ストレスと抗酸化能の変化 と神経学的予後 (2012)
  • Author(s): 石川浩平、井上貴昭、角由佳、岡本健、田中裕
  • Organizer: 第40回日本救急医学会総会
  • Place of Presentation: 京都
• [Presentation] Nucleotides as prognostic factors for post-cardiac arrest syndrome (2012)
  • Author(s): Sumi Y, Ishikawa K, Inoue Y, Okamoto K, Tanaka H, Lee L, Junger WG
  • Organizer: Resuscitation Science Symposium
  • Place of Presentation: Los Angels, California