Yx. Li et al., Up-regulated intragraft gene expression, ICAM-1 and IL-2R molecules, and apoptotic epithelial cells during rejection of rat small intestine allografts, CHIN MED J, 114(10), 2001, pp. 1089-1094
Objective To investigate the kinetics and the magnitude of intragraft gene
expression of interleukin-2 (IL-2), interferon-gamma (IFN-gamma), perforin
and granzyme B, and intragraft expression of interleukin-2 receptor (IL-213
) and intercellular adhesion molecule-1 (ICAM-1) during acute rejection epi
sodes, and to analyze the changes in apoptosis in small intestinal allograf
Methods Heterotopic small intestine transplantation was performed with inbr
ed rats F344/N (RT1(1)) and Wistar/A (RT1-A(k), RT1-E-d). All recipients we
re divided into four groups: group 1: Wistar, native control; group 2: Wist
ar --> Wistar; group 3: F344 --> Wistar and group 4: F344 --> Wistar + cycl
osporine A (6 mg . kg(-1) . d(-1) I. M.). The grafts were harvested on post
operative days (PODs) 3, 5 and 7. All samples were examined pathologically.
Intragraft mRNA expression of IL-2, IFN-gamma, perforin and granzyme B wer
e detected with reverse transcriptase polymerase chain reaction (RT-PCR) an
d intragraft expression of IL-213 and ICAM-1 were stained using immunohisto
chemistry. We also analyzed the change in apoptosis rejection with terminal
deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL).
Results Mild acute rejection occurred on POD 3 in the allograft group, mode
rate acute rejection on POD 5, and severe acute rejection on POD 7, while n
one of the isografts had histological evidence of acute rejection. Cyclospo
rine A could effectively control rejection. Gene expression was virtually n
egative in the native control. Only on POD 5 was IL-2 mRNA expression of al
lografts significantly higher than that of isografts ( P < 0.05). IFN-gamma
mRNA expression was significantly higher than that of the control groups (
P< 0.01) on PODs 3, 5 and 7, and the level of perforin and granzyme B mRNA
expression reached significantly higher levels than in the other two contr
ol groups on POD 5 and POD 7. Intragraft IL-2R expression of the allograft
was significantly higher than that of the other three control groups. Only
on POD 3 was intragraft ICAM-1 expression of allografts significantly highe
r than isografts. The number of apoptotic cells per crypt of allografts was
significantly higher than that of the other three control groups on POD 3
and POD 5 (P <less than> 0.01).
Conclusion Transcription of IL-2, IFN-,gamma, perforin and granzyme B, and
expression of IL-213 and ICAM-1 as well as apoptosis of epithelial cells of
the grafts play an important role in small intestine allograft rejection.
Intragraft gene expression of IFN-gamma and intragraft expression of IL-2R
as well as apoptotic epitheliall cells may become a specific and sensitive
diagnostic method of clinical value. Furthermore, therapeutic strategies to
alter these molecules in small intestine transplantation may improve the o
utcome of current antirejection therapy.