Molecular mechanisms of neutrophil functions critical in lung injury

中性粒细胞向肺的募集在肺炎、败血症、胃内容物误吸和呼吸机诱导的肺损伤引起的肺部炎症和急性肺损伤（ALI）的发展中起着至关重要的作用。在基线条件下，中性粒细胞倾向于通过未知的机制回到肺部。在酸诱导的ALI和细菌脂多糖诱导的肺部炎症中，中性粒细胞的募集被加速和增强。在ALI的发展过程中，不同类型的细胞释放许多促炎趋化因子和细胞因子，调节中性粒细胞募集和血管通透性。我们将研究三个目标：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亚型对中性粒细胞向肺募集的重要性；3)12/15脂氧合酶加重肺损伤的分子机制。本研究旨在确定在哪些治疗干预措施旨在抑制中性粒细胞募集和肺损伤可能是可行的。

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.