K. Urata et al., Role of Kupffer cells in the survival after rat liver transplantation withlong portal vein clamping times, TRANSPLAN I, 13(6), 2000, pp. 420-427
Applying the orthotopic rat river transplantation (ORLT) model, postoperati
ve survival has been shown to be mainly dependent on the portal vein clampi
ng time (PVCT). It was hypothesized that prolonged intestinal congestion wa
s responsible for the activation of Kupffer cells (KC) with overproduction
of TNF, secondary to splanchnic endotoxin accumulation and release on reper
fusion. The role of KCs was directly investigated in the context of long PV
CTs by eliminating them (using liposome-encapsulated dichloromethylene diph
osphonate), by preventing their activation (using a calcium channel blocker
nisoldipine) and by inhibiting TNF production (using thalidomide). Livers
from different groups of rats were transplanted following 24-h cold preserv
ation in the UW solution with long PVCTs (from 18-21 min). KCs depletion, p
reservation with nisoldipine and pretreatment with thalidomide significantl
y improved survival in conditions using long PVCTs. KC depletion and nisold
ipine preservation had no effect on liver enzymes or pathological findings
while lung injury was significantly improved. The present data confirm that
, in the context of ORLT with long PVCTs, KCs are directly responsible for
the systemic endotoxin-like shock syndrome and their effect is mediated thr
ough overproduction of TNF.