San Francisco VA Medical Center, University of California San Francisco, San Francisco, California, USA.
Am J Pathol. 2011 Sep;179(3):1081-7. doi: 10.1016/j.ajpath.2011.05.017. Epub 2011 Jul 8.
The removal of edema from the air spaces is a critical function of the alveolar barrier requiring intact tight junctions. Alveolar fluid clearance contributes to graft function after transplantation and is associated with survival in patients with acute lung injury. Claudin-4 concentrations are known to increase during lung injury and the loss of claudin-4 decreases alveolar fluid clearance in mice. This study was therefore undertaken to evaluate whether differences in lung expression of the tight junction protein claudin-4 are associated with alveolar fluid clearance or clinical measures of lung function. Alveolar fluid clearance rates were measured in ex vivo perfused human lungs not used for transplantation and were compared with histological lung injury and clinical measures of lung injury in the donors. Claudin-4 staining demonstrated a positive correlation with alveolar fluid clearance (Spearman rank correlation [r(s)] = 0.71; P < 0.003); however, claudin-4 staining was not strongly associated with histological measures of lung injury. The expression of other tight junction proteins (including ZO-1) was not associated with alveolar fluid clearance or claudin-4 levels. Claudin-4 staining was lower in lungs from donors with greater impairment in respiratory physiology. These data suggest that claudin-4 may promote alveolar fluid clearance and demonstrate that the amount of claudin-4 expressed may provide specific information regarding alveolar epithelial barrier function that strengthens the link between histological changes and physiological impairment.
清除肺泡腔中的水肿是肺泡屏障的一个关键功能，需要完整的紧密连接。肺泡液体清除有助于移植后的移植物功能，并与急性肺损伤患者的生存相关。已知在肺损伤期间 Claudin-4 浓度增加，Claudin-4 的丢失会降低小鼠的肺泡液体清除率。因此，本研究旨在评估肺泡紧密连接蛋白 Claudin-4 的肺表达差异是否与肺泡液体清除率或肺功能的临床指标相关。在未用于移植的离体灌注人肺中测量肺泡液体清除率，并与供体的组织学肺损伤和肺损伤的临床指标进行比较。Claudin-4 染色与肺泡液体清除率呈正相关（Spearman 秩相关 [r(s)]=0.71；P<0.003）；然而，Claudin-4 染色与组织学肺损伤指标的相关性不强。其他紧密连接蛋白（包括 ZO-1）的表达与肺泡液体清除率或 Claudin-4 水平无关。呼吸生理功能受损较大的供体肺中的 Claudin-4 染色较低。这些数据表明 Claudin-4 可能促进肺泡液体清除，并表明表达的 Claudin-4 量可能提供有关肺泡上皮屏障功能的具体信息，从而加强组织学变化与生理损伤之间的联系。
