Lipocalin 2 is protective against E. coli pneumonia.
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.
Wu
Hong
H
Granulocyte Research Laboratory, Rigshospitalet, Copenhagen, Denmark.
Santoni-Rugiu
Eric
E
Ralfkiaer
Elisabeth
E
Porse
Bo T
BT
Moser
Claus
C
Høiby
Niels
N
Borregaard
Niels
N
Cowland
Jack B
JB
D000209:Acute-Phase Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D056809:Alveolar Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000517:prevention & control*; D005260:Female; D005291:Ferrichrome / Q000008:administration & dosage; D007113:Immunity, Innate; D007150:Immunohistochemistry; D000071068:Lipocalin-2; D054834:Lipocalins / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000378:metabolism* / Q000382:microbiology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015513:Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018410:Pneumonia, Bacterial / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000517:prevention & control*; D020545:Respiratory Mucosa / Q000378:metabolism / Q000382:microbiology; D017262:Siderophores / Q000008:administration & dosage; D013997:Time Factors
D000209:Acute-Phase Proteins; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; D017262:Siderophores; C071332:Lcn2 protein, mouse; D005291:Ferrichrome; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse