Hepatic stellate cells may be potential effectors of platelet activating factor induced portal hypertension.
OBJECTIVE
To determine platelet activating factor (PAF) receptor expression in cirrhotic hepatic stellate cells.


METHODS
Hepatic stellate cells, isolated from the livers of control and CCl(4)-induced cirrhotic rats, were placed in serum-free medium after overnight culture. We determined the PAF receptor in hepatic stellate cells by saturation binding technique and semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR), and the effects of PAF and its antagonist BN52021 on prostaglandin E(2) (PGE(2)) release by stellate cells.


RESULTS
Scatchard analysis indicated the presence of PAF receptor with dissociation constant (Kd) of 4.66 nmol/L and maximum binding capacity (Bmax) of 24.65 fmol/microg in cirrhotic stellate cells. Compared with the control, the maximum PAF binding capacity increased significantly (Bmax: 24.65 +/- 1.96 fmol/microg. DNA, R = 0.982 vs 5.74 +/- 1.55 fmol/microg. DNA, R = 0.93; P < 0.01), whereas receptor affinity had no significant difference (Kd of 4.66 +/- 0.33 nmol/L for the cirrhosis and 3.51 +/- 0.26 nmol/L for the control; P > 0.05). Consistent with the receptor binding data, the mRNA expression of PAF receptor was increased significantly in cirrhotic stellate cells. PAF in a concentration-dependent manner induced PGE(2) synthesis in cirrhotic hepatic stellate cells, but the effects were blocked significantly by BN52021.


CONCLUSIONS
Cirrhosis sensitizes hepatic stellate cells to PAF by elevating its receptor level and hepatic stellate cells maybe potential effectors of PAF induced portal hypertension.
Chen
Yan
Y
Department of Gastroenterology, 302 Hospital of PLA, 100 Xisihuan Middle Road, Beijing 100039, China.
Wang
Chun-Ping
CP
Lu
Yin-Ying
YY
Zhou
Lin
L
Su
Shu-Hui
SH
Jia
Hong-Jun
HJ
Feng
Yong-Yi
YY
Yang
Yong-Ping
YP
D000818:Animals; D022781:Hepatocytes / Q000473:pathology / Q000502:physiology*; D006975:Hypertension, Portal / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000378:metabolism* / Q000473:pathology; D008297:Male; D010972:Platelet Activating Factor / Q000378:metabolism*; D010980:Platelet Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*
D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor