S. Arii et al., PATHOGENIC ROLE OF KUPFFER CELL ACTIVATION IN THE REPERFUSION INJURY OF COLD-PRESERVED LIVER, Transplantation, 58(10), 1994, pp. 1072-1077
The present study was designed to investigate the possible participati
on of Kupffer cells in the development of reperfusion injury of the co
ld-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 e
levation of the effluent levels of GOT and LDH significantly, and that
pretreatment with a Kupffer cell inhibitor, gadolinium chloride, inhi
bited 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 we
re primed by cold preservation with Euro-Collins solution, and then ac
tivated when the reperfusion was done. It seems likely that the Kupffe
r cell activation induced by cold preservation/reperfusion plays a maj
or role in reperfusion injury with sinusoidal micro circulatory distur
bance, and that TNF alpha is responsible for the impairment of the rep
erfused liver graft.