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- Title
Lipcalin 2 is protective against E. coli pneumonia.
- Authors
Hong Wu; Santoni-Rugiu, Eric; Ralfkiaer, Elisabeth; Porse, Bo T.; Moser, Claus; Høiby, Niels; Borregaard, Niels; Cowland, Jack B.
- Abstract
Background: Lipocalin 2 is a bacteriostatic protein that binds the siderophore enterobactin, an iron-chelating molecule produced by Escherichia coli (E. coli) that is required for bacterial growth. Infection of the lungs by E. coli is rare despite a frequent exposure to this commensal bacterium. Lipocalin 2 is an effector molecule of the innate immune system and could therefore play a role in hindering growth of E. coli in the lungs. Methods: Lipocalin 2 knock-out and wild type mice were infected with two strains of E. coli. The lungs were removed 48 hours post-infection and examined for lipocalin 2 and MMP9 (a myeloid marker protein) by immunohistochemical staining and western blotting. Bacterial numbers were assessed in the lungs of the mice at 2 and 5 days after infection and mortality of the mice was monitored over a five-day period. The effect of administering ferrichrome (an iron source that cannot be bound by lipocalin 2) along with E.coli was also examined. Results: Intratracheal installation of E. coli in mice resulted in strong induction of lipocalin 2 expression in bronchial epithelium and alveolar type II pneumocytes. Migration of myeloid cells to the site of infection also contributed to an increased lipocalin 2 level in the lungs. Significant higher bacterial numbers were observed in the lungs of lipocalin 2 knock-out mice on days 2 and 5 after infection with E. coli (p < 0.05). In addition, a higher number of E. coli was found in the spleen of surviving lipocalin 2 knock-out mice on day 5 post-infection than in the corresponding wild-type mice (p < 0.05). The protective effect against E. coli infection in wild type mice could be counteracted by the siderophore ferrichrome, indicating that the protective effect of lipocalin 2 depends on its ability to sequester iron. Conclusions: Lipocalin 2 is important for protection of airways against infection by E. coli.
- Subjects
ESCHERICHIA coli; PNEUMONIA; FOODBORNE diseases; ANTIBACTERIAL agents; IMMUNOHISTOCHEMISTRY
- Publication
Respiratory Research, 2010, Vol 11, p96
- ISSN
1465-9921
- Publication type
Article
- DOI
10.1186/1465-9921-11-96