Hepatic leukostasis and hypoxic stress in adhesion molecule-deficient mice after gut ischemia/reperfusion.
The concept that leukocyte-endothelial cell adhesion (LECA) is a major determinant of the tissue injury elicited by ischemia/reperfusion (I/R) is largely based on studies employing adhesion molecule-specific monoclonal antibodies. The objective of this study was to assess the contribution of LECA to I/R injury using mutant mice (all on a C57B1 background) that are deficient in either intracellular adhesion molecule-1, P-selectin, or CD11/CD18. The accumulation of fluorescently labeled leukocytes and the number of nonperfused sinusoids in livers of control and adhesion molecule-deficient mice were monitored by intravital microscopy for 1 h after release of the occluded (for 15 min) superior mesenteric artery. Autofluorescence of pyridine nucleotide (NADH) was measured as an indicator of mitochondrial O2 consumption and redox status. The number of stationary leukocytes in the liver after gut I/R was significantly elevated compared with baseline values in C57B1 (control) mice. Autofluorescence of NADH was also significantly increased (indicating hypoxia) after I/R in these mice, especially in the pericentral region. Intercellular adhesion molecule-1-, CD11/CD18-, and P-selectin-deficient mice all exhibited a blunted leukosequestration response to I/R and smaller increments in nonperfused sinusoids, relative to C57B1 mice. All adhesion molecule-deficient mice also exhibited an attenuated increment in NADH autofluorescence in the pericentral region, relative to control mice. These results from adhesion molecule-deficient mice provide additional support for the view that LECA is an important determinant of the liver dysfunction induced by gut I/R.
Horie
Y
Y
Department of Physiology, Louisiana State University Medical Center, Shreveport 71130, USA.
Wolf
R
R
Anderson
D C
DC
Granger
D N
DN
D000818:Animals; D000860:Hypoxia / Q000503:physiopathology*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D018921:Leukostasis / Q000503:physiopathology*; D008099:Liver / Q000098:blood supply*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008833:Microcirculation / Q000503:physiopathology; D015427:Reperfusion Injury / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D013312:Stress, Physiological / Q000503:physiopathology*
D018799:Intercellular Adhesion Molecule-1