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.

采用大鼠腹膜炎和内毒素团注两种不同炎症模型，观察枯否细胞(KCs)在急性肺损伤中的作用。此外，还研究了KCs和组织巨噬细胞(MφS)在表型和功能上的差异。大鼠于注射内毒素前24小时给予GdCl3，观察24小时存活率。在另一组实验中，大鼠在盲肠结扎和穿孔(CLP)前24小时给予KC毒物生理盐水或氯化Gd(GdCl3)。术后7天评估患者的生存情况。GdCl3可完全阻止LPS团注后肺微血管通透性的增加和死亡率的增加。另一方面，GdCl3处理增加了肺损伤，降低了存活率。此外，通过表型分析，根据大小和吞噬功能将KCs划分为3个亚群。此外，组织MφS对内毒素的反应也存在功能差异。因此，KCs和组织MφS对内毒素的异质性反应导致某些细胞因子和趋化因子的产生，从而影响肺功能。此外，KCs在急性肺损伤中的作用依赖于炎症过程中的病理生理条件。

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。