Overexpression of α1-acid glycoprotein in transgenic mice leads to sensitisation to acute colitis

被引:25
作者
Hochepied, T
Wullaert, A
Berger, FG
Baumann, H
Brouckaert, P
Steidler, L
Libert, C
机构
[1] State Univ Ghent, Dept Mol Biol, B-9000 Ghent, Belgium
[2] Flanders Interuniv Inst Biotechnol, Ghent, Belgium
[3] Univ S Carolina, Dept Biol Sci, Columbia, SC 29208 USA
[4] Roswell Pk Canc Inst, Dept Mol & Cellular Biol, Buffalo, NY 14263 USA
关键词
D O I
10.1136/gut.51.3.398
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background: alpha(i)-Acid glycoprotein (alpha(1)-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 alpha(1)-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 alpha(1)-AGP in the development of IBD. Methods: Dextran sodium sulphate (DSS) 2% was added to the drinking water of transgenic mice, overexpressing the rat alpha(1)-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 alpha(1)-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 alpha(1)-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 alpha(1)-AGP result in a more aggressive development of acute colitis.
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页码:398 / 404
页数:7
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