Challenging study to clarify mechanisms of multiple organ failure

阐明多器官衰竭机制的挑战性研究

• 批准号: 24659802
• 负责人: TANAKA Hiroshi
• 金额: $ 2.41万
• 依托单位: Juntendo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-24659802/
• 关键词: 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

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.

ATP参与细胞内和细胞外信号传导。中性粒细胞（PMN）在炎症反应中起着关键作用。脓毒症患者血浆ATP水平和CD 11b水平均显著高于健康对照组，且CD 11b水平与血浆ATP水平相关。这些数据表明，ATP从受损细胞或激活的炎症细胞释放通过ATP受体刺激PMN并触发脓毒症中的炎症。脓毒症引起的DIC与高死亡率相关。观察脓毒症并发DIC患者中性粒细胞（PMN）功能和变形能力的变化。我们阐明了中性粒细胞的变形性和活化与脓毒症引起的DIC的严重程度相关。建立了人中性粒细胞（PMNs）中ATP的化学传感器（PMAP-1、MitoAP-1）荧光成像。该方法将有助于了解ATP在PMN中的动力学，并阐明其在炎症中的多种生理功能。

项目成果

Plasma ATP levels and outcome of sepsis

血浆 ATP 水平和脓毒症的结果

• 发表时间: 2013
• 作者: 末吉孝一郎;角由佳;角由佳;角由佳;角由佳
• 通讯作者: 角由佳

Plasma ATP is required for neutrophil activation in a mouse sepsis model.

小鼠败血症模型中嗜中性粒细胞激活需要血浆ATP。

• DOI: 10.1097/shk.0000000000000180
• 发表时间: 2014-08
• 期刊: Shock (Augusta, Ga.)
• 作者: Sumi Y;Woehrle T;Chen Y;Bao Y;Li X;Yao Y;Inoue Y;Tanaka H;Junger WG
• 通讯作者: Junger WG

Recombinant human soluble thrombomodulin in sepsis-induced disseminated intravascular coagulation: a multicenter propensity score analysis.

• DOI: 10.1007/s00134-013-2822-2
• 发表时间: 2013-04
• 期刊: INTENSIVE CARE MEDICINE
• 影响因子: 38.9
• 作者: Yamakawa, Kazuma;Ogura, Hiroshi;Fujimi, Satoshi;Morikawa, Miki;Ogawa, Yoshihito;Mohri, Tomoyoshi;Nakamori, Yasushi;Inoue, Yoshiaki;Kuwagata, Yasuyuki;Tanaka, Hiroshi;Hamasaki, Toshimitsu;Shimazu, Takeshi
• 通讯作者: Shimazu, Takeshi

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

开发用于创伤患者生物侵入性评估的新生物标志物

• 发表时间: 2013
• 作者: 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
• 通讯作者: 田中裕

血漿中ATPを経時的に測定した重症急性膵炎の1例

严重急性胰腺炎一例，随时间测量血浆 ATP

• 发表时间: 2012
• 作者: 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
• 通讯作者: 田中裕