Challenging study to clarify mechanisms of multiple organ failure

2013 Fiscal Year Final Research Report

• 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
• Keywords: 多臓器不全 / 敗血症 / DAMPｓ / ATP / 白血球機能 / 蛍光イメージング

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
  • 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] 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] 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
• [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
  • Year and Date: 20140200
• [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
  • Year and Date: 20140200
• [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
  • Year and Date: 20131000
• [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
  • Year and Date: 20131000
• [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
  • Year and Date: 20131000
• [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
  • Year and Date: 20131000
• [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
  • Year and Date: 20130700
• [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
  • Year and Date: 20130600
• [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
  • Year and Date: 20130500