title: The extracellular matrix: an early target of preservation/reperfusion injury and acute rejection after small bowel transplantation.
abstract: BACKGROUND
  Endothelial cells are known to be an early target of preservation/reperfusion injury and acute rejection, whereas the extracellular matrix (ECM) may also play an equally important role in the sequelae of both events.
  
  
  METHODS
  Syngeneic and allogeneic rat small bowel transplantations (SBTX) were performed after 6 hr of preservation. Animals were subsequently killed at defined time points for determination of ECM parameters within the graft and in plasma.
  
  
  RESULTS
  Laminin levels were significantly increased 20 min after reperfusion (syngeneic SBTX: 357+/-65.9 ng/ml; allogeneic SBTX: 361+/-79.6 ng/ml; P< or =0.01). After syngeneic transplantation, laminin levels normalized by postoperative day (POD) 7, whereas there was a rejection-induced increase after allogeneic SBTX (POD 7: 179+/-60.1 ng/ml; POD 9: 333+/-13.6 ng/ml; P< or =0.01 vs. syngeneic SBTX). This increase was accompanied by an increase in tumor necrosis factor-alpha levels at POD 9. Hyaluronic acid levels were significantly elevated after 24 hr (syngeneic SBTX: 1086+/-176 microg/L; allogeneic SBTX: 918+/-108 microg/L; P< or =0.01). After syngeneic SBTX, hyaluronic acid levels normalized by POD 7, whereas persistently higher levels were observed after allogeneic SBTX. Immunohistochemistry confirmed early changes (20 min after reperfusion) at the ECM. Anti-laminin and anti-CD44 staining normalized at POD 5 after syngeneic SBTX. After allogeneic SBTX, rejection-specific changes were evident with anti-laminin staining commencing on POD 5 and progressing until POD 9. At similar time points, increased expression of fibronectin- and interferon-gamma-positive material was evident.
  
  
  CONCLUSIONS
  The ECM can be considered to be an early target of preservation/reperfusion injury and acute rejection. Plasma parameters reliably reflected the changes observed within the graft. Laminin and hyaluronic acid levels may be used as indicators of initial graft function. Furthermore, the increase in laminin levels was an early indicator of acute rejection. Determination of these parameters may significantly improve monitoring after SBTX.
authors.affiliation: Department of Surgery, Virchow Clinic, Humboldt University of Berlin, Germany.
authors.forename: A R
authors.initials: AR
authors.lastname: Mueller
authors.forename: K P
authors.initials: KP
authors.lastname: Platz
authors.forename: C
authors.initials: C
authors.lastname: Heckert
authors.forename: M
authors.initials: M
authors.lastname: Häusler
authors.forename: O
authors.initials: O
authors.lastname: Guckelberger
authors.forename: D
authors.initials: D
authors.lastname: Schuppan
authors.forename: H
authors.initials: H
authors.lastname: Lobeck
authors.forename: P
authors.initials: P
authors.lastname: Neuhaus
mesh_terms: D000818:Animals; D005109:Extracellular Matrix / Q000502:physiology*; D006084:Graft Rejection; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D007421:Intestine, Small / Q000637:transplantation*; D007797:Laminin / Q000378:metabolism; D008297:Male; D009926:Organ Preservation; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000503:physiopathology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018960:Hyaluronan Receptors; D007797:Laminin; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D006820:Hyaluronic Acid