Acute rejection in allogeneic rodent small bowel transplantation causes smooth muscle dysfunction via an inflammatory response within the intestinal muscularis.
BACKGROUND
Isogeneic intestinal transplantation elicits an inflammatory response within the intestinal muscularis that is associated with dysmotility. Usually the inflammation and the postoperative motor dysfunction resolve within a few days after small bowel transplantation (SBTx). However, the onset of acute rejection in allogeneic SBTx is again associated with dysmotility. We hypothesized that dysmotility during acute rejection is based on coexpression of kinetically active mediators by the alloreactive leucocyte infiltrate.


METHODS
Rat SBTx (BN to Lew and BN to BN) was performed without immunosuppression. Animals were sacrificed at 1, 4, and 7 days after SBTx. Leukocyte infiltration was investigated in muscularis whole mounts by immunohistochemistry. Mediator mRNA expression was determined by reverse transcriptase polymerase chain reaction. Muscle contractility was assessed in a standard organ bath.


RESULTS
Transplanted animals showed a significant inflammatory response within the muscularis at day 1 after SBTx. However, allogeneic transplanted animals exhibited a significant second inflammatory peak at day 7 (mRNA induction: iNOS 150-fold; tumor necrosis factor-alpha 18-fold; interferon-gamma 397-fold), parallel to the onset of rejection. This change was associated with a significant leukocyte infiltration. Compared to controls, allogeneic transplanted animals showed a 29% decrease in smooth muscle contractility on days 1 and 4 and a 71% decrease of contractility on postoperative day 7.


CONCLUSIONS
The motor dysfunction of transplanted small bowel during acute rejection is associated with an inflammatory reaction in the intestinal muscularis. The initial unspecific inflammation process immediately after transplantation is reactivated and intensified during acute rejection.
Schaefer
N
N
Department of Surgery, Rheinische Friedrich-Wilhelms-Universität, Sigmund-Freud-Strasse 25, D-53105 Bonn, Germany. tuerler@uni-bonn.de
Tahara
K
K
Websky
M v
Mv
Kalff
J C
JC
Hirner
A
A
Türler
A
A
D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics; D006084:Graft Rejection / Q000503:physiopathology*; D007249:Inflammation / Q000503:physiopathology*; D007371:Interferon-gamma / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D007422:Intestines / Q000637:transplantation*; D009130:Muscle, Smooth / Q000503:physiopathology*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D014184:Transplantation, Homologous / Q000276:immunology / Q000473:pathology*; D014185:Transplantation, Isogeneic / Q000276:immunology / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II