Up-Regulation of ICAM-1 During Cold Ischemia Triggers Early Neutrophil Infiltration in Human Pancreas Allograft Reperfusion

Abstract

Background Graft pancreatitis is induced by ischemia/reperfusion injury in which neutrophil infiltration is believed to be a crucial early event. This observation suggests the presence of adhesion molecules already at the time of reperfusion. Therefore, this study was performed to evaluate the pattern of ICAM-1 and P-Selectin expression on human pancreas allografts following cold ischemia and reperfusion. Patients and Methods We performed an analysis of pancreas biopsy specimens taken from 13 patients undergoing pancreas transplantation compared with pancreas specimens from 10 patients following resection. Cryostat sections were stained with monoclonal antibodies against CD11b, a neutrophil marker, and the adhesion molecules ICAM-1 and P-Selectin. Results Extensive infiltration of CD11b-positive cells was detected in venules and capillaries of pancreas allografts after reperfusion (18.38 ± 0.87) compared with controls (T1 4.22 ± 0.55) or with tissue specimens at about 10 hours of cold ischemia (2.60 ± 0.35; P < .001). Similarly, the pattern of P-Selectin showed a moderate expression before organ harvest (1.54 ± 0.21) and in samples during cold ischemia (1.46 ± 0.24) followed by a significantly greater number of P-Selectin–positive cells after reperfusion (2.54 ± 0.18; P = .005). ICAM-1 was only weakly expressed on the surface of the venular endothelium in all controls (0.77 ± 0.12). In contrast to P-Selectin, ICAM-1 showed prominent up-regulation during cold ischemia (2.23 ± 0.23; P < .001) with no further increase after reperfusion (2.23 ± 0.17). Conclusion The data suggested that ICAM-1 was already up-regulated during cold ischemia, possibly representing the mechanism of early neutrophil infiltration observed in human pancreatic ischemia/reperfusion injury.