ICAM-1 UP-REGULATION IN DISTANT TISSUES AFTER HEPATIC ISCHEMIA REPERFUSION - A CLUE TO THE MECHANISM OF MULTIPLE ORGAN FAILURE/

Background/Purpose: Endothelial cell adhesion molecules (ECAMs) are fe lt to play an important role in ischemia/ reperfusion (I/R) injury by causing adhesion of leukocytes to endothelial cells. It is possible th at ECAMs play a role in multiple organ system failure. ICAM-1 is one o f the adhesion molecules that has been shown to be upregulated in resp onse to cytokines. This upregulation leads to leukocyte endothelial ce ll interaction (adhesion) and to neutrophil infiltration of the affect ed tissue. The purpose of our study was to measure ICAM-1 expression i n the liver and other organs after hepatic ischemia/reperfusion (I/R). Methods: A laparotomy was performed on 14 Sprague-Dawley rats; 45 min utes of occlusive ischemia to the left lateral lobe was followed by 5 hours of reperfusion. The rat was injected with I-125-labeled ICAM-1 M Ab and I-131-labeled nonbinding MAb (to control for nonspecific accumu lation of ICAM-1 MAb). Entire organs were harvested and accumulated ac tivity was measured in each organ. ICAM-1 levels were expressed as per cent injected dose per gram of tissue. Control animals underwent sham laparotomy. Results: ICAM-1 was upregulated in the ischemic lobe of th e liver, nonischemic lobe of the liver, heart, kidney, intestine, and pancreas. Up-regulation in the lung was not significant. Both the lung and liver had high constitutive levels of ICAM-1. Conclusions: These data show that (1) significant hepatic upregulation of ICAM-1 after he patic ischemia/reperfusion and (2) significant ICAM-1 upregulation in other tissues (heart, kidney, and intestine) after hepatic ischemia/re perfusion. The ICAM-1 upregulation in distant organs is likely mediate d by cytokines such as tumor necrosis factor (TNF). These data show th at leukocyte endothelial cell interactions in distant organs may be me diated by hepatic ischemia/reperfusion. This is a possible explanation for how failure of one organ can lead to failure of others in multipl e organ system failure. Copyright (C) 1998 by W,B. Saunders Company.