Gut 2002 Sep;51(3):398-404
Overexpression of alpha(1)-acid glycoprotein in transgenic mice leads to sensitisation to acute colitis.
Hochepied T, Wullaert A, Berger FG, Baumann H, Brouckaert P, Steidler L, Libert C.
Flanders Interuniversity Institute for Biotechnology and University of Ghent, Department of Molecular Biology, 9000 Ghent, Belgium.
BACKGROUND: alpha(1)-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.