In situ determination by surface chemiluminescence of temporal relationships between evolving warm ischemia-reperfusion injury in rat liver and phagocyte activation and recruitment.
Liver ischemia-reperfusion is characterized by an increased oxygen-dependent free radical chain-reaction rate and an increased steady-state concentration of reactive oxygen species. The aim of this study was to evaluate the in situ generation of reactive oxygen species and its relationship with phagocyte activation and recruitment in reperfused rat liver. Rat livers were subjected to 2 hours of selective lobular ischemia and reperfusion for up to 12 hours. The following parameters were determined: in situ liver chemiluminescence, understood to reflect the tissue steady-state concentration of singlet oxygen ((1)O(2)); myeloperoxidase tissue activity; the number of neutrophils; and the degree of necrosis. An early chemiluminescence burst was measured after 30 minutes of blood reflow (early phase of oxidative stress), followed by a relapse and a further increase after 4 to 12 hours of reperfusion (late phase of oxidative stress). Both early and late phases were modified by pretreatment with gadolinium chloride (GdCl(3)), pointing to a key role of the Kupffer cells. Neutrophils infiltrated into the liver, myeloperoxidase activity, in situ chemiluminescence, and necrosis were found to be strongly correlated over the 4- to 12-hour reperfusion period (r =.960; average of the 4 correlation coefficients). Together with resident phagocytes, neutrophil recruitment and activation appear to provide a major contribution to the increase of oxygen-dependent free-radical reactions and amplification of liver reperfusion damage. Surface chemiluminescence appears to properly describe the in situ and in vivo progressive organization of the acute inflammatory response with phagocyte-mediated liver injury.
Cutrìn
J C
JC
Department of Clinical and Biological Sciences, University of Turin, ASL San Luigi Gonzaga, Orbassano, Turin, Italy. juan.cutrin@unito.it
Boveris
A
A
Zingaro
B
B
Corvetti
G
G
Poli
G
G
D000818:Animals; D007511:Ischemia / Q000276:immunology / Q000503:physiopathology*; D008099:Liver / Q000098:blood supply* / Q000276:immunology / Q000503:physiopathology; D008163:Luminescent Measurements; D008297:Male; D008854:Microscopy, Electron; D009336:Necrosis; D018375:Neutrophil Activation; D018384:Oxidative Stress; D010100:Oxygen / Q000032:analysis; D010586:Phagocytes / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000276:immunology / Q000503:physiopathology*; D026082:Singlet Oxygen
D026082:Singlet Oxygen; D010100:Oxygen