Molecular mechanisms of neutrophil functions critical in lung injury

中性粒细胞功能在肺损伤中至关重要的分子机制

• 批准号: 223566930
• 负责人: Professor Dr. Alexander Zarbock
• 金额: --
• 依托单位: Klinik für Anästhesiologie, operative Intensivmedizin und Schmerztherapie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2012
• 资助国家: 德国
• 起止时间: 2011-12-31 至 2016-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/223566930?language=en
• 关键词: Molecular; mechanisms; neutrophil; functions; critical

Neutrophil recruitment into the lung is of critical importance in the development of pulmonary inflammation and acute lung injury (ALI) caused by pneumonia, sepsis, aspiration of gastric content, and ventilator-induced lung injury. Under baseline conditions, neutrophils have a propensity to home to the lung through unknown mechanisms. Neutrophil recruitment is accelerated and enhanced during acid-induced ALI and bacterial lipopolysaccharide induced pulmonary inflammation. During the development of ALI many pro-inflammatory chemokines and cytokines are released by different cell types which modulate neutrophil recruitment and vascular permeability. The proposal consists of three aims in which we will investigate: 1) the molecular mechanisms by which platelet-neutrophil interactions result in TXA2 production and acute lung injury, 2) the importance of the three PAK isoforms for neutrophil recruitment into the lung, and 3) the molecular mechanisms by which 12/15 lipoxygenase exacerbates lung injury. This research is designed to identify points at which therapeutic interventions aimed at curbing neutrophil recruitment and lung injury may be feasible.

中性粒细胞进入肺在肺炎、脓毒症、胃内容物吸入和呼吸机诱导的肺损伤所致的肺部炎症和急性肺损伤(ALI)的发生发展中起着至关重要的作用。在基线条件下，中性粒细胞有通过未知机制归巢到肺的倾向。在酸致ALI和细菌脂多糖诱导的肺部炎症过程中，中性粒细胞募集加速和增强。在ALI的发展过程中，不同类型的细胞会释放许多促炎的趋化因子和细胞因子，调节中性粒细胞的募集和血管通透性。该提案包括三个目标，我们将在其中研究：1)血小板-中性粒细胞相互作用导致TXA2产生和急性肺损伤的分子机制，2)三种PAK亚型对中性粒细胞重新聚集到肺内的重要性，以及3)12/15脂氧合酶加重肺损伤的分子机制。这项研究旨在确定旨在抑制中性粒细胞募集和肺损伤的治疗干预措施可能可行的点。