A monoclonal antibody against ICAM-1 suppresses hepatic ischemia-reperfusion injury in rats.
Since intercellular adhesion molecule-1 (ICAM-1) has been reported to play a major role in reperfusion injury after ischemia, we estimated the effects of an anti-rat ICAM-1 monoclonal antibody (1A29) on hepatic ischemia-reperfusion injury in rats. Partial liver ischemia was achieved by clamping hepatic hilar vessels supplying the cephalad three lobes of the liver for 90 min. An intraportal injection of 1A29 was given 5 min after revascularization (n = 28), and saline was injected in control rats (n = 28). Changes in the proportion of liver necrosis, hepatic tissue blood flow, serum liver enzymes and liver neutrophil sequestration were analyzed at 6, 24, 48 and 72 h after revascularization. The intraportal injection of 1A29 significantly reduced the hepatocellular necrosis, restored the hepatic tissue blood flow at 24, 48 and 72 h of reperfusion (p < 0.05 or p < 0.01), and significantly suppressed the levels of serum liver enzymes at all time points during reperfusion (p < 0.01, respectively). The 1A29 treatment significantly reduced the number of neutrophils at the pericentral area, while those at the periportal area were similar in the two groups. The results suggested that ICAM-1 plays an important role in the development of hepatic ischemia-reperfusion injury, and that 1A29 reduced the injury possibly caused by cytotoxic inflammatory responses, based on neutrophil adherence to pericentral sinusoids.
Kuzume
M
M
Department of Surgery, Showa University Fujigaoka Hospital, Yokohama, Japan.
Nakano
H
H
Yamaguchi
M
M
Matsumiya
A
A
Shimokohbe
G
G
Kitamura
N
N
Nagasaki
H
H
Kumada
K
K
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D007511:Ischemia / Q000150:complications*; D008099:Liver / Q000098:blood supply*; D008297:Male; D009504:Neutrophils / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*
D000911:Antibodies, Monoclonal; D018799:Intercellular Adhesion Molecule-1; D000410:Alanine Transaminase