Pathogenic role of Kupffer cell activation in the reperfusion injury of cold-preserved liver.
The present study was designed to investigate the possible participation of Kupffer cells in the development of reperfusion injury of the cold-stored liver graft. In the cold preservation of Kupffer cells with Euro-Collins solution, the proportion of asialo-GM1-positive cells was significantly increased at 12 and 24 hr of storage, and the TNF alpha-producing activity in these cells was approximately fivefold greater than control. Northern blot analysis demonstrated that TNF alpha mRNA was remarkably elevated in the reperfusion of the cold-preserved liver, although that of the prereperfused graft was only slightly induced. The reperfusion experiments of the cold-stored liver graft showed that addition of anti-TNF alpha antibody to the perfusate suppressed the elevation of the effluent levels of GOT and LDH significantly, and that pretreatment with a Kupffer cell inhibitor, gadolinium chloride, inhibited the increase of these enzymes in the effluents almost completely. Histological study revealed deposition of a fibrinlike substance in the sinusoid and the central veins extensively in the reperfused liver graft, whereas no apparent deposition was observed in the gadolinium-pretreated liver. Thus, the present study showed that Kupffer cells were primed by cold preservation with Euro-Collins solution, and then activated when the reperfusion was done. It seems likely that the Kupffer cell activation induced by cold preservation/reperfusion plays a major role in reperfusion injury with sinusoidal microcirculatory disturbance, and that TNF alpha is responsible for the impairment of the reperfused liver graft.
First Department of Surgery, Faculty of Medicine, Kyoto University, Japan.
S
S
Arii
K
K
Monden
Y
Y
Adachi
W
W
Zhang
H
H
Higashitsuji
M
M
Furutani
M
M
Mise
S
S
Fujita
T
T
Nakamura
M
M
Imamura
D000410:Alanine Transaminase / Q000032:analysis; D000818:Animals; D000906:Antibodies / Q000627:therapeutic use; D002470:Cell Survival; D003080:Cold Temperature; D005677:G(M1) Ganglioside / Q000032:analysis; D007728:Kupffer Cells / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008099:Liver / Q000098:blood supply* / Q000201:enzymology; D009926:Organ Preservation; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D015427:Reperfusion Injury / Q000209:etiology* / Q000517:prevention & control; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D000906:Antibodies; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside; D007770:L-Lactate Dehydrogenase; D000410:Alanine Transaminase