PT  - JOURNAL ARTICLE
AU  - G.J.W. van der Windt
AU  - J.J. Hoogerwerf
AU  - A.F. de Vos
AU  - S. Florquin
AU  - T. van der Poll
TI  - Osteopontin promotes host defense during <em>Klebsiella pneumoniae</em>-induced pneumonia
AID  - 10.1183/09031936.00002710
DP  - 2010 Dec 01
TA  - European Respiratory Journal
PG  - 1337--1345
VI  - 36
IP  - 6
4099  - http://erj.ersjournals.com/content/36/6/1337.short
4100  - http://erj.ersjournals.com/content/36/6/1337.full
SO  - Eur Respir J2010 Dec 01; 36
AB  - 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.