Regulation of postischemic liver injury following different durations of ischemia.
The objective of this study was to define the relationship among Kupffer cells, O(2)(-) production, and TNF-alpha expression in the pathophysiology of postischemic liver injury following short and long periods of ischemia. Using different forms of superoxide dismutase with varying circulating half-lives, a monoclonal antibody directed against mouse TNF-alpha, and NADPH oxidase-deficient mice, we found that 45 or 90 min of partial (70%) liver ischemia and 6 h of reperfusion (I/R) produced time-dependent increases in liver injury and TNF-alpha expression in the absence of neutrophil infiltration. Furthermore, we observed that hepatocellular injury induced by short periods of ischemia were not dependent on formation of TNF-alpha but were dependent on Kupffer cells and NADPH oxidase-independent production of O(2)(-). However, liver injury induced by extended periods of ischemia appeared to require the presence of Kupffer cells, NADPH oxidase-derived O(2)(-), and TNF-alpha expression. We conclude that the sources for O(2)(-) formation and the relative importance of TNF-alpha in the pathophysiology of I/R-induced hepatocellular injury differ depending on the duration of ischemia.
Hines
Ian N
IN
Department of Molecular and Cellular Physiology, LSU Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130, USA.
Hoffman
Jason M
JM
Scheerens
Heleen
H
Day
Brian J
BJ
Harada
Hirohisa
H
Pavlick
Kevin P
KP
Bharwani
Sulaiman
S
Wolf
Robert
R
Gao
Bifeng
B
Flores
Sonia
S
McCord
Joe M
JM
Grisham
Matthew B
MB
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D006498:Hepatectomy; D006801:Humans; D007511:Ischemia / Q000473:pathology*; D007728:Kupffer Cells / Q000473:pathology; D008099:Liver / Q000473:pathology*; D008102:Liver Circulation / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D019255:NADPH Oxidases / Q000235:genetics; D010101:Oxygen Consumption / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; D000410:Alanine Transaminase