Leukocyte adhesion and hepatic microvascular responses to intestinal ischemia/reperfusion in rats.
OBJECTIVE
Although it has been reported that gut ischemia/reperfusion (I/R) elicits neutrophil-dependent liver dysfunction, little is known about the kinetics of leukocyte accumulation in the hepatic microcirculation after gut I/R. The aim of this study was to determine the temporal relationship between leukocyte sequestration and oxidative stress in rat liver after occlusion (30 minutes) and reperfusion (60 minutes) of the superior mesenteric artery and assess the effects of neutrophil depletion or immunoneutralization of either intercellular adhesion molecule 1 (ICAM-1) or the leukocyte adhesion glycoprotein CD11/CD18 on the hepatic microvascular responses to gut I/R.


METHODS
Leukocyte accumulation, number of nonperfused sinusoids, and autofluorescence of reduced nicotinamide adenine dinucleotide (NADH) were monitored using intravital videomicroscopy both before and after gut I/R.


RESULTS
The number of adherent leukocytes in both midzonal and pericentral regions after gut I/R was elevated. Autofluorescence of NADH increased after reperfusion (indicating hypoxia), particularly in the pericentral region. Neutrophil depletion or antibodies to either ICAM-1 or CD11/CD18 blunted the gut I/R-induced increases in NADH autofluorescence in the pericentral region, leukocyte adherence, and nonperfused sinusoids.


CONCLUSIONS
Leukocytes accumulate in the liver after gut I/R via interaction of CD11/CD18 and ICAM-1. The leukocytes appear to mediate an oxidative stress, occurring in proximity to nonperfused sinusoids, that may contribute to liver injury.
Horie
Y
Y
Department of Physiology, Louisiana State University Medical Center, Shreveport, USA.
Wolf
R
R
Miyasaka
M
M
Anderson
D C
DC
Granger
D N
DN
D000818:Animals; D000911:Antibodies, Monoclonal; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D005453:Fluorescence; D007422:Intestines / Q000098:blood supply*; D007511:Ischemia / Q000378:metabolism / Q000503:physiopathology*; D007962:Leukocytes / Q000502:physiology*; D008102:Liver Circulation; D008297:Male; D008833:Microcirculation; D009243:NAD / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D009243:NAD