Nguyen MyTrang, Pace Amy J, Koller Beverly H
Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.
J Exp Med. 2007 Jun 11;204(6):1383-93. doi: 10.1084/jem.20061205. Epub 2007 May 21.
The contribution of the Na(+)-K(+)-Cl(-) transporter (NKCC1) to fluid in ion transport and fluid secretion in the lung and in other secretory epithelia has been well established. Far less is known concerning the role of this cotransporter in the physiological response of the pulmonary system during acute inflammation. Here we show that mice lacking this transporter are protected against hypothermic sepsis and bacteremia developing as a result of Klebsiella pneumoniae infection in the lung. In contrast, this protection was not observed in NKCC1(-/-) mice with K. pneumoniae-induced peritonitis. Although overall recruitment of cells to the lungs was not altered, the number of cells present in the airways was increased in the NKCC1(-/-) animals. Despite this robust inflammatory response, the increase in vascular permeability observed in this acute inflammatory model was attenuated in the NKCC1(-/-) animals. Our studies suggest that NKCC1 plays a unique and untoward unrecognized role in acute inflammatory responses in the lung and that specific inhibition of this NKCC isoform could be beneficial in treatment of sepsis.
钠 - 钾 - 氯转运体（NKCC1）在肺部及其他分泌上皮细胞的离子转运和液体分泌中所起的作用已得到充分证实。然而，关于该协同转运体在急性炎症期间肺部系统生理反应中的作用，人们所知甚少。在此我们表明，缺乏这种转运体的小鼠可免受因肺炎克雷伯菌肺部感染而引发的低温败血症和菌血症的影响。相比之下，在肺炎克雷伯菌诱导的腹膜炎的NKCC1（-/-）小鼠中未观察到这种保护作用。尽管整体向肺部募集的细胞数量未改变，但在NKCC1（-/-）动物的气道中存在的细胞数量增加。尽管有这种强烈的炎症反应，但在该急性炎症模型中观察到的血管通透性增加在NKCC1（-/-）动物中有所减弱。我们的研究表明，NKCC1在肺部急性炎症反应中起独特且未被认识到的不良作用，并且特异性抑制这种NKCC亚型可能对败血症治疗有益。
