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.
Arii
S
S
First Department of Surgery, Faculty of Medicine, Kyoto University, Japan.
Monden
K
K
Adachi
Y
Y
Zhang
W
W
Higashitsuji
H
H
Furutani
M
M
Mise
M
M
Fujita
S
S
Nakamura
T
T
Imamura
M
M
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