ICAM-1 upregulation in distant tissues after hepatic ischemia/reperfusion: a clue to the mechanism of multiple organ failure.
OBJECTIVE
Endothelial cell adhesion molecules (ECAMs) are felt to play an important role in ischemia/reperfusion (I/R) injury by causing adhesion of leukocytes to endothelial cells. It is possible that ECAMs play a role in multiple organ system failure. ICAM-1 is one of the adhesion molecules that has been shown to be upregulated in response to cytokines. This upregulation leads to leukocyte endothelial cell interaction (adhesion) and to neutrophil infiltration of the affected tissue. The purpose of our study was to measure ICAM-1 expression in the liver and other organs after hepatic ischemia/reperfusion (I/R).


METHODS
A laparotomy was performed on 14 Sprague-Dawley rats; 45 minutes of occlusive ischemia to the left lateral lobe was followed by 5 hours of reperfusion. The rat was injected with I125-labeled ICAM-1 MAb and I131-labeled nonbinding MAb (to control for nonspecific accumulation of ICAM-1 MAb). Entire organs were harvested and accumulated activity was measured in each organ. ICAM-1 levels were expressed as percent injected dose per gram of tissue. Control animals underwent sham laparotomy.


RESULTS
ICAM-1 was upregulated in the ischemic lobe of the 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 hepatic ischemia/reperfusion and (2) significant ICAM-1 upregulation in other tissues (heart, kidney, and intestine) after hepatic ischemia/reperfusion. The ICAM-1 upregulation in distant organs is likely mediated by cytokines such as tumor necrosis factor (TNF). These data show that leukocyte endothelial cell interactions in distant organs may be mediated by hepatic ischemia/reperfusion. This is a possible explanation for how failure of one organ can lead to failure of others in multiple organ system failure.
Meyer
K
K
Department of Surgery and Physiology, Louisiana State University Medical Center-Shreveport, 71130-3932, USA.
Brown
M F
MF
Zibari
G
G
Panes
J
J
McMillan
R W
RW
McDonald
J C
JC
Granger
D N
DN
D000818:Animals; D000911:Antibodies, Monoclonal; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D007457:Iodine Radioisotopes; D008099:Liver / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000378:metabolism; D009102:Multiple Organ Failure / Q000209:etiology*; D011877:Radionuclide Imaging; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism*; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; D018799:Intercellular Adhesion Molecule-1