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Virchows Archiv

, Volume 455, Issue 3, pp 225–233 | Cite as

Neutrophil gelatinase-associated lipocalin (NGAL/Lcn2) is upregulated in gastric mucosa infected with Helicobacter pylori

  • Warner Alpízar-AlpízarEmail author
  • Ole Didrik Laerum
  • Martin Illemann
  • José A. Ramírez
  • Adriana Arias
  • Wendy Malespín-Bendaña
  • Vanessa Ramírez
  • Leif R. Lund
  • Niels Borregaard
  • Boye Schnack Nielsen
Original Article

Abstract

Helicobacter pylori infection is one of the most significant risk factors for gastric cancer. The infection is established early in life and persists lifelong leading to a sustained chronic inflammation. Iron is essential for most living organisms. Bacteria use several mechanisms to acquire iron from their hosts, including the synthesis of the potent iron chelators known as siderophores. Hosts cells may express the siderophore-binding protein neutrophil gelatinase-associated lipocalin (NGAL/lipocalin-2 (Lcn2)) in response to infection, thus preventing bacterial iron uptake. We have characterized here the pattern of expression of NGAL/Lcn2 in gastric mucosa (45 non-neoplastic and 38 neoplastic tissue samples) and explored the connection between NGAL/Lcn2 expression and H. pylori infection. Immunohistochemical analysis showed high NGAL/Lcn2 expression in normal and gastritis-affected mucosa compared to low expression in intestinal metaplasia, dysplasia, and gastric cancer. In normal and gastritis-affected mucosa (n = 36 tissue samples), NGAL/Lcn2 was more frequently seen in epithelial cells located at the neck and base of the glands in H. pylori-positive cases than in similar epithelial cells of noninfected cases (Fisher’s exact test, p = 0.04). In conclusion, the high expression of NGAL/Lcn2 in normal and gastritis-affected mucosa infected with H. pylori suggests that NGAL/Lcn2 is upregulated locally in response to this bacterial infection. It is discussed whether this may have a causal relation to the development of gastric cancer.

Keywords

NGAL/Lcn2 Helicobacter pylori Inflammation Gastritis Intestinal metaplasia Gastric cancer 

Abbreviations

IM

Intestinal metaplasia

mAb

Monoclonal antibody

pAbs

Polyclonal antibodies

TNP

Trinitrophenyl hapten

NGAL

Neutrophil gelatinase-associated lipocalin

Lcn2

Lipocalin-2

Notes

Acknowledgements

We thank Ms. Öznur Turan and Ms. Agnieszka Ingvorsen for their excellent technical assistance and Mr. John Post for his photographic assistance. This study was supported by the Danish Cancer Society, the Lundbeck Foundation, Haukeland University Hospital (Helse-Vest), and Vicerrectoría de Investigación of the University of Costa Rica.

Conflict of interest statement

We declare that we have no conflict of interest.

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Warner Alpízar-Alpízar
    • 1
    • 2
    • 3
    • 8
    Email author
  • Ole Didrik Laerum
    • 1
  • Martin Illemann
    • 3
  • José A. Ramírez
    • 4
  • Adriana Arias
    • 4
  • Wendy Malespín-Bendaña
    • 2
  • Vanessa Ramírez
    • 2
  • Leif R. Lund
    • 5
  • Niels Borregaard
    • 6
  • Boye Schnack Nielsen
    • 3
    • 7
  1. 1.The Gade Institute, University of Bergen and Department of PathologyHaukeland University HospitalBergenNorway
  2. 2.Cancer Research Program, Health Research Institute (INISA)University of Costa RicaSan JoséCosta Rica
  3. 3.The Finsen LaboratoryCopenhagenDenmark
  4. 4.Department of PathologyDr. Rafael A. Calderón Guardia HospitalSan JoséCosta Rica
  5. 5.Department of Biology, Section for Cell and Developmental BiologyUniversity of CopenhagenCopenhagenDenmark
  6. 6.The Granulocyte Research Laboratory, Department of HaematologyUniversity of CopenhagenCopenhagenDenmark
  7. 7.Exiqon A/S, Diagnostic Product DevelopmentVedbækDenmark
  8. 8.The Gade Institute, Department of PathologyHaukeland University HospitalBergenNorway

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