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Overexpression of α1-acid glycoprotein in transgenic mice leads to sensitisation to acute colitis
  1. T Hochepied1,
  2. A Wullaert1,
  3. F G Berger2,
  4. H Baumann3,
  5. P Brouckaert1,
  6. L Steidler1,
  7. C Libert1
  1. 1Flanders Interuniversity Institute for Biotechnology and University of Ghent, Department of Molecular Biology, 9000 Ghent, Belgium
  2. 2University of South Carolina, Department of Biological Sciences, Columbia, SC 29208, USA
  3. 3Roswell Park Cancer Institute, Department of Molecular and Cellular Biology, Buffalo, NY 14263, USA
  1. Correspondence to:
    Dr C Libert, Department of Molecular Biology, KL Ledeganckstraat 35, B-9000 Ghent, Belgium;


Background: α1-Acid glycoprotein (α1-AGP) is an acute phase protein in most mammalian species whose concentration rises 2–5-fold during an acute phase reaction. Its serum concentration has often been used as a marker of disease, including inflammatory bowel disease (IBD). High α1-AGP levels were found to have a prognostic value for an increased risk of relapse in IBD.

Aims: To investigate a possible role for increased serum levels of α1-AGP in the development of IBD.

Methods: Dextran sodium sulphate (DSS) 2% was added to the drinking water of transgenic mice, overexpressing the rat α1-AGP gene, to induce acute colitis, thus mimicking the conditions of relapse. Clinical parameters, inflammatory parameters, and histological analyses on colon sections were performed.

Results: Homozygous α1-AGP-transgenic mice started losing weight and showed rectal bleeding significantly earlier than heterozygous transgenic or wild-type mice. Survival time of homozygous transgenic mice was significantly shorter compared with heterozygous and wild-type mice. The higher susceptibility of homozygous α1-AGP-transgenic mice to DSS induced acute colitis was also reflected in higher local myeloperoxidase levels, higher inflammation scores of the colon, and higher systemic levels of interleukin 6 and serum amyloid P component. Local inflammatory parameters were also significantly different in heterozygous transgenic mice compared with wild-type mice, indicating a local dosage effect. In homozygous transgenic mice, significantly higher amounts of bacteria were found in organs but IgA levels were only slightly lower than those of control mice.

Conclusion: Sufficiently high serum levels of α1-AGP result in a more aggressive development of acute colitis.

  • acute phase proteins
  • dextran sodium sulphate
  • inflammatory bowel disease
  • interleukin
  • liver
  • IL, interleukin
  • α1-AGP
  • α1-acid glycoprotein
  • DSS, dextran sodium sulphate
  • IBD, inflammatory bowel disease
  • MPO, myeloperoxidase
  • PBS, phosphate buffered saline
  • SAP, serum amyloid P component
  • TNF, tumour necrosis factor

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