Local anesthetic interactions with host defense mechanisms of human neutrophils - effects on signaling of chemotaxis, oxidative burst and phagocytosis.

局部麻醉剂与人类中性粒细胞宿主防御机制的相互作用 - 对趋化性、氧化爆发和吞噬作用信号的影响。

• 批准号: 35163745
• 负责人: Dr. Annette Ploppa
• 金额: --
• 依托单位: Department of Anesthesiology
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2007
• 资助国家: 德国
• 起止时间: 2006-12-31 至 2007-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/35163745?language=en
• 关键词: Local; anesthetic; interactions; host; defense

The systemic application of local anesthetics (LA) intra- and postoperatively results in an amelioration of several inflammation-mediated disorders. E.g. the duration of postoperative ileus been shown to be drastically reduced by intravenous lidocaine administration in patients with major abdominal surgery.In vitro, we have probed mechanisms of action on immunocompetent cells. One target identified is the Gq protein, which is inhibited in a time-dependent and reversible manner by low concentrations of local anesthetics. This inhibition of Gq protein function seems to be responsible for the ability of local anesthetics to inhibit priming of extracellular superoxide release. However, the neutrophil response to injury has many aspects, and for other key functions of the host defense we only have rather superficial information as to their local anesthetic sensitivity.The purpose of this project is to clarify, if LA modulate key functions of the host defense (leukocyte chemotaxis, phagocytosis and oxidative burst) by the same intracellular pathway of Gq protein inhibition as already shown for superoxide release and if the inhibtion of these leukocyte functions is also time dependent.

术中和术后全身应用局部麻醉剂（LA）可改善几种炎症介导的疾病。例如，在腹部大手术患者中，静脉注射利多卡因可显著减少术后肠梗阻的持续时间。在体外，我们探索了对免疫活性细胞的作用机制。确定的一个靶点是Gq蛋白，其以时间依赖性和可逆的方式被低浓度的局部麻醉剂抑制。这种Gq蛋白功能的抑制似乎是负责的局部麻醉剂的能力，以抑制引发的细胞外超氧化物释放。然而，中性粒细胞对损伤的反应是多方面的，对于宿主防御的其他关键功能，我们只有相当肤浅的信息，如局部麻醉剂的敏感性。本项目的目的是澄清，如果LA调节宿主防御的关键功能，（白细胞趋化性，吞噬作用和氧化爆发）通过相同的细胞内Gq蛋白抑制途径，如已经显示的超氧化物释放，如果这些白细胞功能的抑制也是时间依赖性的。