96. Jahrestagung der Deutschen Gesellschaft für Pathologie e. V ...

prognostic impact was found in rectal cancer patients. The association
of lymphatic invasion with the number of examined tissue blocks is an
important finding that should be considered establishing practice guidelines
for pathologic work-up of cancer specimens.
FR-P-073
Inflammatory bowel diseases (IBD) are associated with decreased
colonic expression of PEPT1 in humans and mice
T . Wuensch 1 , S . Schulz2 , N . Schaltenberg1 , N . Lill1 , D . Haller1 , H . Daniel1 1Technische Universität München, ZIEL – Research Center for Nutrition and
Food Science, Freising-Weihenstephan, 2Charité – Universitätsmedizin
Berlin, Pathology, Berlin
Aims. The intestinal peptide transporter PEPT1 is found in the brush border
membrane of enterocytes in the small intestine where it contributes
to amino acid absorption from luminal protein digestion. Beside that,
PEPT1 is proposed to be aberrantly expressed during colonic inflammation.
Because of its capability to transport bacteria-derived chemotacticacting
agents such as fMLP (formyl-methionyl-leucine-phenylalanine),
MDP (muramyl dipeptide) or L-Ala-D-Glu-meso-DAP, PEPT1 might act
as an amplifier of inflammation. However, a systematic analysis of PEPT1
expression along the healthy colon has never been described. Here we
provide information on PEPT1 mRNA and protein expression along the
healthy colon of different species and during intestinal inflammation.
Methods. PEPT1 mRNA and protein expression levels were determined
by qRT-PCR, immunofluorescence and Western blotting, respectively,
in intestinal samples from healthy mice, rats and humans. Furthermore,
germ-free mice and three mouse models, resembling Crohn’s-like ileitis
(TNFdeltaARE/WT) and colitis (IL-10-/-, IL- 10XTLR2-/-) as well as intestinal
tissue samples from IBD patients were analyzed by immunohistochemistry.
PEPT1 function in colon was determined by transport studies
using [14C]-Glycyl-sarcosine (Gly-Sar). Moreover, the susceptibility
of PEPT1-deficient (Pept1-/-) mice to dextran sodium sulfate (DSS)-induced
colitis was investigated.
Results. Colonic PEPT1 expression showed a distinct pattern of distribution
with marked differences between proximal and distal segments.
No PEPT1 expression was detectable in the proximal colon but prominent
expression was found from mid colon to rectum of mice rats and
humans. Functional Gly-Sar uptake rates were highest in jejunum and
distal colon (19.76 nmol/20 min/mg protein vs. 1.71–0.42 nmol/20 min/
mg protein) and significantly lower (p