Investigation of heterogeneity of tissue macrophages and inflammatory immune response during infection.

感染过程中组织巨噬细胞异质性和炎症免疫反应的研究。

• 批准号: 15591394
• 负责人: KONO Hiroshi
• 金额: $ 2.24万
• 依托单位: University of Yamanashi
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591394/
• 关键词: Kupffer cell; acute lung injury; peritonitis; endotoxin; cytokine; chemokine

The role of Kupffer cells (KCs) in acute lung injury was investigated in two different inflammatory models, peritonitis and endotoxin bolus infusion models, in rats. Furthermore, phenotypic and functional differences in KCs and tissue macrophages (Mφs) were also investigated. Rats were given GdCl_3 24 hours prior to LPS administration, and survival rate was assessed for 24 hours. In another set of experiments, rats were given saline or gadolinium chloride (GdCl_3), a KC toxicant, 24 hours before cecal ligation and puncture (CLP). Survival was assessed for 7 days after CLP. GdCl_3 completely prevented increases in lung microvascular permeability and mortality after LPS bolus infusion. On the other hand, GdCl_3 treatment increased lung injury and reduced the survival rate. Furthermore, from phenotypic analysis, KCs were divided into 3 subpopulations based on size and phagocytosis. Moreover, functional differences were observed in response of tissue Mφs to endotoxin. Thus, the heterogeneous response of KCs and tissue Mφs to endotoxin leads to production of certain cytokines and chemokines that affect lung function. Furthermore, the role of KCs in acute lung injury depends on pathophysiological condition during inflammation.

在两种不同的炎症模型，腹膜炎和内毒素注入模型中，研究了库普弗细胞（KCS）在急性肺损伤中的作用。此外，还研究了KC和组织巨噬细胞（Mφ）的表型和功能差异。在LPS施用前24小时给予大鼠GDCL_3，并评估24小时的存活率。在另一套实验中，在Cecal结扎和穿刺前24小时（CLP）给予大鼠盐水或氯化盐（GDCL_3）。在CLP后评估生存期7天。 GDCL_3完全阻止了LPS注入后肺微血管通透性和死亡率的增加。另一方面，GDCL_3治疗增加了肺损伤并降低了存活率。此外，根据表型分析，KC根据大小和吞噬作用将3个亚群体分为3个亚群。此外，在组织MφS对内毒素的反应中观察到功能差异。这，KC和组织Mφ对内毒素的异质反应导致产生影响肺功能的某些细胞因子和趋化因子。此外，KC在急性肺损伤中的作用取决于炎症期间的病理生理状况。

项目成果

Kono H et al.: "Medium-chain triglycerides modulate inflammatory immune response in the gut in rats administered endotoxin"American Journal of Physiology. (In press). (2004)

Kono H 等人：“中链甘油三酯调节施用内毒素的大鼠肠道中的炎症免疫反应”美国生理学杂志。

Protective effects of medium-chain triglycerides on the liver and the gut in rats administered endotoxin.

中链甘油三酯对给予内毒素的大鼠的肝脏和肠道的保护作用。

• 发表时间: 2003
• 期刊: Ann Surg 237
• 作者: Takahashi Y;et al.;Kono H et al.
• 通讯作者: Kono H et al.

Medium-chain triglycerides modulate inflammatory immune response in the gut in rats administered endotoxin.

中链甘油三酯调节内毒素大鼠肠道内的炎症免疫反应。

• 发表时间: 2004
• 期刊: Am J Physiol Gastrointest Liver Physiol 286
• 作者: Kono H et al.

Kono H et al.: "Edaravone, a Novel Free Radical Scavenger, Prevents Liver Injury and Mortality in Rats Administered Endotoxin"Journal of Pharmacology and Experimental Therapeutics. 307. 74-82 (2003)

Kono H 等人：“依达拉奉，一种新型自由基清除剂，可预防内毒素大鼠的肝损伤和死亡”药理学和实验治疗学杂志。