Molecular mechanisms of neutrophil functions critical in lung injury

肺内的神经元募集在肺炎、脓毒症、胃内容物吸入和呼吸机诱导的肺损伤引起的肺部炎症和急性肺损伤（ALI）的发展中至关重要。在基线条件下，中性粒细胞倾向于通过未知机制归巢至肺。在酸诱导的ALI和细菌脂多糖诱导的肺部炎症过程中，神经元的募集加速并增强。在ALI的发展过程中，许多促炎趋化因子和细胞因子由不同类型的细胞释放，其调节中性粒细胞募集和血管通透性。该提案包括三个目标，我们将调查：1）血小板-中性粒细胞相互作用导致TXA 2产生和急性肺损伤的分子机制，2）三种PAK亚型对中性粒细胞招募到肺中的重要性，以及3）12/15脂氧合酶加剧肺损伤的分子机制。本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可能可行的点。

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.