title: Acute rejection and the muscularis propria after intestinal transplantation: the alloresponse, inflammation, and smooth muscle function.
abstract: BACKGROUND
  It has been shown that in transplantation the intestinal muscularis may act as an immunologically active layer via the activation of resident macrophages and the recruitment of leukocytes. Thus we hypothesized that inflammation within the intestinal muscularis is involved in the promotion of acute rejection in intestinal allografts and that this causes smooth muscle dysfunction.
  
  
  METHODS
  Orthotopic allogenic and small bowel transplantation (Brown-Norway rats-Lewis rats) was performed without immunosuppression. Animals were sacrificed 1, 4, and 7 days after small bowel transplantation. Isogenic transplanted grafts (Brown-Norway rats-Brown-Norway rats) as well as nontransplanted bowel served as controls. Mediator mRNA expression was determined by real-time reverse-transcriptase polymerase chain reaction. Leukocyte infiltration was evaluated in muscularis whole mounts by immunohistochemistry. Apoptosis was evaluated by TdT-mediated dUTP-X nick end labeling assay. Contractility was assessed in a standard organ bath under bethanechol stimulation. Statistical analysis was performed using a Student's t test and one-way analysis of variance.
  
  
  RESULTS
  Transplanted animals showed a significant early inflammatory response within the graft muscularis because of reperfusion injury. Only allogenic transplanted animals exhibited a significant second molecular inflammatory peak in the muscularis during rejection (mRNA induction for interleukin (IL)-6, intercellular adhesion molecule-1, monocyte chemoattractant protein (MCP)-1, interferon-gamma, IL-2, tumor necrosis factor-alpha, IL-10, inducible nitric oxide synthase). These findings were associated with significant leukocyte infiltration within the muscularis, increasing apoptotic cells and massive impairment of smooth muscle contractile activity by 78%.
  
  
  CONCLUSIONS
  The data shows that transplantation results in an early and temporary inflammatory response within the intestinal graft muscularis, that is reactivated and intensified during acute allograft rejection. The immunoreaction within the intestinal muscularis leads to intestinal allograft smooth muscle dysfunction.
authors.affiliation: Department of Surgery, Rheinische Friedrich-Wilhelms-Universität, Bonn, Germany. nico.schaefer@ukb.uni-bonn.de
authors.forename: Nico
authors.initials: N
authors.lastname: Schaefer
authors.forename: Kazunori
authors.initials: K
authors.lastname: Tahara
authors.forename: Martin V
authors.initials: MV
authors.lastname: Websky
authors.forename: Arne
authors.initials: A
authors.lastname: Koscielny
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Pantelis
authors.forename: Jörg C
authors.initials: JC
authors.lastname: Kalff
authors.forename: Kareem
authors.initials: K
authors.lastname: Abu-Elmagd
authors.forename: Andreas
authors.initials: A
authors.lastname: Hirner
authors.forename: Andreas
authors.initials: A
authors.lastname: Türler
mesh_terms: D000208:Acute Disease; D000818:Animals; D018723:Bethanechol / Q000494:pharmacology; D006084:Graft Rejection / Q000473:pathology*; D007249:Inflammation / Q000209:etiology; D007422:Intestines / Q000473:pathology / Q000637:transplantation*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000473:pathology / Q000503:physiopathology / Q000637:transplantation; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D014184:Transplantation, Homologous / Q000473:pathology*; D014185:Transplantation, Isogeneic / Q000473:pathology
chemical_list: D018723:Bethanechol; D009195:Peroxidase