Osteopontin promotes host defense during Klebsiella pneumoniae-induced pneumonia

G J W Van Der Windt,A F De Vos,J J Hoogerwerf,S Florquin,T Van Der Poll

doi:10.1183/09031936.00002710

Abstract

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.

Highlights

Wild-type (WT) and OPN knockout (KO) mice were intranasally infected with 104 colony forming units of K. pneumoniae, or administered Klebsiella lipopolysaccharides (LPS)
Osteopontin levels are increased during K. pneumoniae infection To obtain a first insight into a potential role for OPN during gram-negative pneumonia, we measured OPN concentrations in bronchoalveolar lavage fluid (BALF), lung and plasma from WT mice before infection and 6, 24 and 48 h after infection with 104 colony-forming units (CFU) K. pneumoniae
Osteopontin limits pulmonary bacterial growth To determine whether OPN affected mortality due to Klebsiella pneumonia, we followed WT and OPN KO mice for 14 days after K. pneumoniae infection

Summary

Introduction

Wild-type (WT) and OPN knockout (KO) mice were intranasally infected with 104 colony forming units of K. pneumoniae, or administered Klebsiella lipopolysaccharides (LPS). Recombinant OPN (rOPN) was intranasally administered to WT and CD44 KO mice. During Klebsiella pneumonia, WT mice displayed elevated pulmonary and plasma OPN levels. Neutrophil recruitment into the bronchoalveolar space was impaired in the absence of OPN after intrapulmonary delivery of either Klebsiella bacteria or Klebsiella LPS. OPN did not affect K. pneumoniae growth or neutrophil function. OPN levels were rapidly increased in the bronchoalveolar space during K. pneumoniae pneumonia, where OPN serves a chemotactic function towards neutrophils, thereby. Increased in patients with sepsis, the majority of Osteopontin (OPN) is a phosphorylated glycoprotein, expressed by a broad range of tissues whom suffered from pneumonia as the primary source of infection [10]

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