Resolution of inflammation in the human lung: Mechanisms involved in leukocyte egression across the alveolar and bronchial epithelium.

肺部疾病是导致许多发病率和死亡率的原因，目前在欧洲每5人中就有1人死亡。许多肺部疾病，包括慢性阻塞性气道疾病（COPD）、肺炎、流感和某些形式的肺纤维化（PF），其特征在于肺部炎症。白色血细胞或白细胞在体内不断移动以防止感染，但数量过多可能会导致肺部损伤，因此在炎症消退期间有效清除这些细胞至关重要。虽然人们对白细胞如何进入肺部了解很多，但对白细胞如何离开肺部或在患者呼吸时从肺部清除却知之甚少。我们已经证明，白细胞可以通过进入呼吸道而离开肺部，在那里它们可以作为痰被咳出。然而，白细胞也可以进入肺泡，在那里进行气体交换。如果不迅速清除，可能会使患者病情恶化。我们的目标是了解白细胞进入气道或肺泡的调节机制。如果我们了解这一点，那么我们可能能够促进肺部炎症的解决并加速肺部疾病的恢复。我们已经发现，肺细胞上称为ICAM-1和ICAM-2的特定分子是白细胞移动到肺的不同部位所必需的，并且我们已经表明，称为Slits的其他蛋白质可以改变白细胞的迁移。我们还表明，ICAM-1和-2存在于气道之间和肺泡中的不同水平。此外，气道和肺泡之间的裂缝水平存在差异。我们认为，差异表达和调节的关键粘附分子，如ICAM-1和ICAM-2，连同裂缝，作用定位白细胞的气道，而不是肺泡。我们认为，这种定位促进炎症的解决，我们的项目将进一步研究这一点。我们的最终目标是开发新的药物来帮助肺部炎症患者康复。

Lung disease is responsible for much morbidity and mortality and currently kills 1 in 5 people in Europe. Many lung diseases including chronic obstructive airways disease (COPD), pneumonia, influenza, and some forms of pulmonary fibrosis (PF) are characterised by lung inflammation. White blood cells, or leukocytes, travel continuously throughout the body to protect against infection, but in excessive numbers they can result in damage to the lung, and it is essential that these cells are cleared efficiently during the resolution of inflammation. Although much is known of how leukocytes enter the lung, much less is known about how they leave or are cleared from the lung as a patient revoers. We have shown that leukocytes can leave the lung by passing into the airways where they can be coughed up, as phlegm. However, leukocytes may also pass into the alveoli of the lung where gas exchange takes place. If they are not removed quickly they can worsen the condition of the patient. We are aiming to understand what regulations this leukocyte egression into the airways or into the alveoli. If we understand this then we may be able to promote the resolution of lung inflammation and speed the recovery from lung diseases. We have found that specific molecules called ICAM-1 and ICAM-2 on the lung cells are required for leukocytes to move into different parts of the lung and we have shown that other proteins called Slits can alter the migration of the leukocytes. We have also shown that ICAM-1 and -2 are present at different levels between the airways and in the alveoli. In addition there is a difference in levels of Slits between the airways and the alveoli. We suggest that differential expression and regulation of key adhesion molecules such as ICAM-1 and ICAM-2, together with Slits, act to localise leukocytes to the airways instead of the alveoli. We propose that such localisation promotes resolution of inflammation and our project will investigate this further. Our ultimate aim is to develop novel agents to aid recovery of patients with lung inflammation.