Center of Infection and Immunity Amsterdam (CINIMA), University of Amsterdam, Amsterdam, The Netherlands.
Eur Respir J. 2010 Dec;36(6):1337-45. doi: 10.1183/09031936.00002710. Epub 2010 Apr 8.
Klebsiella pneumoniae is a common cause of nosocomial pneumonia. Osteopontin (OPN) is a phosphorylated glycoprotein involved in inflammatory processes, some of which is mediated by CD44. The aim of this study was to determine the role of OPN during K. pneumoniae-induced pneumonia. Wild-type (WT) and OPN knockout (KO) mice were intranasally infected with 10⁴ colony forming units of K. pneumoniae, or administered Klebsiella lipopolysaccharides (LPS). In addition, recombinant OPN (rOPN) was intranasally administered to WT and CD44 KO mice. During Klebsiella pneumonia, WT mice displayed elevated pulmonary and plasma OPN levels. OPN KO and WT mice showed similar pulmonary bacterial loads 6 h after infection; thereafter, Klebsiella loads were higher in lungs of OPN KO mice and the mortality rate in this group was higher than in WT mice. Early neutrophil recruitment into the bronchoalveolar space was impaired in the absence of OPN after intrapulmonary delivery of either Klebsiella bacteria or Klebsiella LPS. Moreover, rOPN induced neutrophil migration into the bronchoalveolar space, independent from CD44. In vitro, OPN did not affect K. pneumoniae growth or neutrophil function. In conclusion, OPN levels were rapidly increased in the bronchoalveolar space during K. pneumoniae pneumonia, where OPN serves a chemotactic function towards neutrophils, thereby facilitating an effective innate immune response.
肺炎克雷伯菌是医院获得性肺炎的常见病因。骨桥蛋白（OPN）是一种参与炎症过程的磷酸化糖蛋白，其中一些是由 CD44 介导的。本研究旨在确定 OPN 在肺炎克雷伯菌诱导性肺炎中的作用。野生型（WT）和 OPN 敲除（KO）小鼠经鼻腔感染 10⁴ 个菌落形成单位的肺炎克雷伯菌，或给予肺炎克雷伯菌脂多糖（LPS）。此外，重组 OPN（rOPN）被鼻腔内给予 WT 和 CD44 KO 小鼠。在肺炎克雷伯菌肺炎期间，WT 小鼠显示出肺和血浆 OPN 水平升高。OPN KO 和 WT 小鼠在感染后 6 小时显示出相似的肺部细菌负荷；此后，OPN KO 小鼠肺部的肺炎克雷伯菌负荷更高，该组的死亡率高于 WT 小鼠。在肺内给予肺炎克雷伯菌或肺炎克雷伯菌 LPS 后，缺乏 OPN 会导致早期中性粒细胞向支气管肺泡空间的募集受损。此外，rOPN 诱导中性粒细胞向支气管肺泡空间迁移，与 CD44 无关。体外，OPN 不影响肺炎克雷伯菌的生长或中性粒细胞的功能。总之，在肺炎克雷伯菌肺炎期间，OPN 水平在支气管肺泡空间中迅速增加，OPN 在此作为向中性粒细胞的趋化因子，从而促进有效的先天免疫反应。
