Lipocalin 2 is protective against E. coli pneumonia

TY - JOUR

T1 - Lipocalin 2 is protective against E. coli pneumonia

AU - Wu, Hong

AU - Santoni-Rugiu, Eric

AU - Ralfkiaer, Elisabeth

AU - Porse, Bo T

AU - Moser, Claus

AU - Høiby, Niels

AU - Borregaard, Niels

AU - Cowland, Jack B

PY - 2010/7/15

Y1 - 2010/7/15

N2 - 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.

AB - 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.

KW - Acute-Phase Proteins

KW - Animals

KW - Blotting, Western

KW - Disease Models, Animal

KW - Escherichia coli

KW - Escherichia coli Infections

KW - Female

KW - Ferrichrome

KW - Immunity, Innate

KW - Immunohistochemistry

KW - Lipocalins

KW - Lung

KW - Matrix Metalloproteinase 9

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Oncogene Proteins

KW - Pneumocytes

KW - Pneumonia, Bacterial

KW - Respiratory Mucosa

KW - Siderophores

KW - Time Factors

U2 - 10.1186/1465-9921-11-96

DO - 10.1186/1465-9921-11-96

M3 - Journal article

C2 - 20633248

SN - 1465-9921

VL - 11

SP - 96

JO - Respiratory Research (Print)

JF - Respiratory Research (Print)

ER -