Augmenter of liver regeneration promotes hepatocyte proliferation induced by Kupffer cells.
OBJECTIVE
To observe the effects of augmenter of liver regeneration (ALR) on Kupffer cells and to determine whether ALR promotes hepatocyte proliferation induced by Kupffer cells.


METHODS
Kupffer cells and hepatocytes were cultured in vitro and various concentrations of recombinant rat ALR (rrALR) were added. 3H-thymidine, BrdU and 3H-leucine incorporation was determined in cultured Kupffer cells and hepatocytes, in hepatocytes conditioned by Kupffer cells, and in associated medium. rrALR was labeled by iodination and used to determine its binding activity by Scatchard analysis in Kupffer cells and primarily cultured rat hepatocytes.


RESULTS
rrALR stimulated DNA replication in Kupffer cells and protein synthesis both in cells and in medium in a non-concentration-dependent manner. The effect was significant at the concentration of 1 microg/L ALR. However, rrALR had no effect on primarily cultured hepatocytes, when hepatocytes were cultured with the Kupffer cell medium conditioned by ALR, DNA replication and protein synthesis in hepatocytes increased significantly at the concentration of 1 microg/L ALR. When the ALR concentration was increased, its effect on hepatocyte proliferation decreased to the basal level. Scatchard analysis indicated the presence of a single class of high affinity receptors with a dissociation constant (Kd) of 0.883 nmol/L and a maximum binding capacity (Bmax) of 126.1 pmol/g protein in the rat Kupffer cells.


CONCLUSIONS
ALR can promote hepatocyte proliferation induced by Kupffer cells, which is associated with the concentration of ALR, suggesting that Kupffer cells play a dual role in liver regeneration.
Wang
Chun-Ping
CP
Department of Gastroenterology, 302 Hospital of Chinese PLA, 100 Xisihuan Middle Road, Beijing 100039, China.
Zhou
Lin
L
Su
Shu-Hui
SH
Chen
Yan
Y
Lu
Yin-Ying
YY
Wang
Fei
F
Jia
Hong-Jun
HJ
Feng
Yong-Yi
YY
Yang
Yong-Ping
YP
D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000737:chemistry; D022781:Hepatocytes / Q000166:cytology / Q000502:physiology*; D006801:Humans; D007728:Kupffer Cells / Q000166:cytology / Q000378:metabolism*; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D050862:Oxidoreductases Acting on Sulfur Group Donors
D017077:Culture Media, Conditioned; D011506:Proteins; D011994:Recombinant Proteins; C088825:GFER protein, rat; D050862:Oxidoreductases Acting on Sulfur Group Donors