THE EXTRACELLULAR-MATRIX - AN EARLY TARGET OF PRESERVATION REPERFUSION INJURY AND ACUTE REJECTION AFTER SMALL-BOWEL TRANSPLANTATION/

Background, Endothelial cells are known to be an early target of prese rvation/reperfusion injury and acute rejection, whereas the extracellu lar matrix (ECM) may also play an equally important role in the sequel ae of both events, Methods. Syngeneic and allogeneic rat small bowel t ransplantations (SBTX) were performed after 6 hr of preservation, Anim als were subsequently killed at defined time points for determination of ECM parameters within the graft and in plasma, Results, Laminin lev els were significantly increased 20 min after reperfusion (syngeneic S BTX: 357+/-65.9 ng/ml; allogeneic SBTX: 361+/-79.6 ng/ml; P less than or equal to 0.01). After syngeneic transplantation, laminin levels nor malized by postoperative day (POD) 7, whereas there was a rejection-in duced increase after allogeneic SBTX (POD 7: 179+/-60.1 ng/ml; POD 9: 333+/-13.6 ng/ml; P less than or equal to 0.01 vs, syngeneic SBTX), Th is increase was accompanied by an increase in tumor necrosis factor-al pha levels at POD 9, Hyaluronic acid levels were significantly elevate d after 24 hr (syngeneic SBTX: 1086+/-176 mu g/L; allogeneic SBTX: 918 +/-108 mu g/L; P less than or equal to 0.01). After syngeneic SBTX, hy aluronic acid levels normalized by POD 7, whereas persistently higher levels were observed after allogeneic SBTX, Immunohistochemistry confi rmed early changes (20 min after reperfusion) at the FCM, Anti-laminin and anti-CD44 staining normalized at POD 5 after syngeneic SBTX, Afte r allogeneic SBTX, rejection-specific changes were evident with antila minin staining commencing on POD 5 and progressing until POD 9, At sim ilar time points, increased expression of fibronectin-and interferon-g amma-positive material was evident, Conclusions, The ECM can be consid ered to be an early target of preservation/reperfusion injury and acut e rejection, Plasma parameters reliably reflected the changes observed within the graft, Laminin and hyaluronic acid levels may be used as i ndicators of initial graft function, Furthermore, the increase in lami nin levels was an early indicator of acute rejection, Determination of these parameters may significantly improve monitoring after SBTX.