Augmentation of the early phase of liver regeneration after 70% partial hepatectomy in rats following selective Kupffer cell depletion.
OBJECTIVE
Kupffer cells are located in the liver sinusoids adjacent to hepatocytes and elaborate a range of growth regulatory molecules involved in regulating hepatocyte proliferation. In vitro observations imply the potential for Kupffer cells to exert both stimulatory and inhibitory influences on hepatocyte DNA synthesis. We aimed to determine the overall effect of Kupffer cell activity during the early regenerative processes after partial hepatectomy.


METHODS
We investigated hepatocyte DNA synthesis, induced by partial hepatectomy in rats, following selective elimination of Kupffer cells by liposome encapsulated dichlormethylene bisphosphonate (Cl2MBP).


RESULTS
We demonstrate that the early phase of liver regeneration was enhanced following Kupffer depletion, as indicated by a greater proportion of hepatocytes undergoing DNA synthesis, and a higher mitotic index. This was associated with an alteration in the balance of growth factors in the liver; HGF and TGFbeta mRNA were reduced in Kupffer cell-depleted animals, and IL-1beta mRNA was absent. In addition, in the absence of partial hepatectomy, the selective depletion of Kupffer cells leads to an increase in the proliferation of hepatocytes in resting liver undergoing DNA synthesis.


CONCLUSIONS
The overall effect of depleting the liver of Kupffer cells is to enhance the proliferation rate of hepatocytes, both after partial hepatectomy and in the resting state.
Department of Medicine, Imperial College School of Medicine, Hammersmith Hospital, London, UK.
R A
RA
Boulton
M R
MR
Alison
M
M
Golding
C
C
Selden
H J
HJ
Hodgson
D000818:Animals; D002455:Cell Division; D004002:Clodronic Acid / Q000008:administration & dosage / Q000633:toxicity; D004247:DNA / Q000096:biosynthesis; D004337:Drug Carriers; D006498:Hepatectomy; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis / Q000235:genetics; D007700:Kinetics; D007728:Kupffer Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008081:Liposomes; D008099:Liver / Q000166:cytology*; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics
D004337:Drug Carriers; D008081:Liposomes; D016212:Transforming Growth Factor beta; D004002:Clodronic Acid; D017228:Hepatocyte Growth Factor; D004247:DNA