Inducible Nitric Oxide Synthase Expression in the Intestinal Muscularis Mediates Severe Smooth Muscle Dysfunction During Acute Rejection in Allogenic Rodent Small Bowel Transplantation

被引:18
作者
Schaefer, Nico [1 ]
Tahara, Kazunori [1 ]
Pech, Thomas [1 ]
Websky, Martin V. [1 ]
Fujishiro, Jun [1 ]
Pantelis, Dimitrios [1 ]
Abu-Elmagd, Kareem [2 ]
Kalff, Jrg C. [1 ]
Hirner, Andreas [1 ]
Tuerler, Andreas [1 ]
机构
[1] Univ Bonn, Dept Surg, Div Gen Visceral Thorac & Vasc Surg, D-53105 Bonn, Germany
[2] Thomas E Starzl Transplantat Inst, Div Intestinal Transplantat, Pittsburgh, PA USA
关键词
intestinal transplantation; acute rejection; iNOS; NO; intestinal muscularis propria; leukocyte infiltrate; macrophages; inflammation; smooth muscle dysfunction;
D O I
10.1016/j.jss.2008.01.019
中图分类号
R61 [外科手术学];
学科分类号
摘要
Background. Acute rejection in small bowel transplantation is associated with dysmotility. Therefore, host and organ not only face the threat of destructive immunological processes but also the risk of bacterial translocation, endotoxemia, and systemic inflammatory response syndrome. We hypothesized that dysmotility during acute rejection is based on an alloreactive leukocyte infiltrate and coexpression. of the kinetically active mediator inducible nitric oxide synthase (iNOS) in the muscularis propria. Materials and methods. Allogenic and isogenic rat small bowel transplantation (SBTx; Brown Norway [BN] to Lewis and BN to BN) was performed without immunosuppression. Animals were sacrificed 4 and 7 d after SBTx. Leukocyte infiltration and iNOS protein was investigated by immunohistochemistry and immunohistology. Real-time reverse transcription polymer chain reaction was used to detect iNOS expression. Griess reaction was used to evaluate NO production. Spontaneous, bethanechol-stimulated, and L-N-6-(1-iminoethyl)-L-Lysin-blocked jejunal circular muscle contractions were measured in a standard organ bath in vitro. Results. On d 7 after SBTx, allogenic transplanted animals showed significant infiltration with ED-1- and ED-2-positive monocytes and macrophages within the muscularis parallel to the manifestation of acute rejection. Additionally, immunohistochemistry localized iNOS protein in leukocytes within the muscularis. Reverse transcription polymer chain reaction showed a significant increase in iNOS mRNA expression (460-fold) in allogenic transplanted muscularis compared to isogenic transplanted muscularis (2.5-fold). Compared to controls, allogenic grafts showed a 73% decrease in smooth muscle contractility, while isogenic grafts showed only an 8% decrease of contractility on d 7. L-N-6-(1-iminoethyl)-L-Lysin application in vitro significantly improved muscle contractility and decreased NO production. Conclusion. The data show that inflammation associated iNOS expression in the intestinal graft muscularis is involved in motoric graft dysfunction during acuterejection. (C) 2008 Elsevier Inc. All rights reserved.
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收藏
页码:159 / 168
页数:10
相关论文
共 49 条
[1]  
Abu-Elmagd K, 2002, Minerva Chir, V57, P543
[2]  
Abu-Elmagd K, 2001, ANN SURG, V234, P404, DOI 10.1097/00000658-200109000-00014
[3]  
Abu-Elmagd Kareem, 2002, Adv Surg, V36, P65
[4]   The influence of surgery, immunosuppressive drugs, and rejection, on graft function after small bowel transplantation: a large-animal study [J].
Alessiani, M ;
De Ponti, F ;
Fayer, F ;
Abbiati, F ;
Zonta, S ;
Zitelli, E ;
Arbustini, E ;
Morbini, P ;
Poggi, N ;
Klersy, C ;
Blangetti, I ;
Dionigi, P ;
Zonta, A .
TRANSPLANT INTERNATIONAL, 2003, 16 (05) :327-335
[5]   Administration of nitric oxide with caspase inhibitors minimizes bacterial translocation in experimental intestinal transplantation [J].
Azuara, D ;
Sola, A ;
Hotter, G ;
Calatayud, L ;
Jaurrieta, E ;
De Oca, J .
TRANSPLANTATION, 2004, 77 (02) :177-183
[6]   Role of nitric oxide in apoptosis and cell necrosis for intestinal transplantation [J].
Azuara, D ;
Sola, A ;
Hotter, G ;
Calatayud, L ;
Jaurrieta, E ;
De Oca, J .
TRANSPLANTATION PROCEEDINGS, 2003, 35 (05) :1931-1932
[7]  
Bauer AJ, 1996, TRANSPLANT P, V28, P2539
[8]   NITRIC-OXIDE MAY BE THE FINAL MEDIATOR OF NONADRENERGIC, NONCHOLINERGIC INHIBITORY JUNCTION POTENTIALS IN THE GUT [J].
CHRISTINCK, F ;
JURY, J ;
CAYABYAB, F ;
DANIEL, EE .
CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY, 1991, 69 (10) :1448-1458
[9]  
Cicalese L, 1996, TRANSPLANT P, V28, P2459
[10]   Interaction between ischemia/reperfusion-induced leukocyte emigration and translocating bacterial enterotoxins on enteric muscle function [J].
Cicalese, L ;
Billiar, TR ;
Rao, AS ;
Bauer, AJ .
TRANSPLANTATION PROCEEDINGS, 1997, 29 (03) :1815-1815