Effects of endothelin on platelet activating factor (PAF) synthesis and release by cultured Kupffer cells from CCl_4-induced cirrhotic rats
- VernacularTitle:内皮素对肝硬化大鼠Kupffer细胞血小板活化因子生成水平的影响
- Author:
Shuhui SU
;
Chunping WANG
;
Yinying LU
- Publication Type:Journal Article
- Keywords:
platelet activating factor;
hypertension,portal;
liver cirrhosis;
Kupffer cells
- From:
Medical Journal of Chinese People's Liberation Army
1982;0(03):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the correlation between Kupffer cells and the synthesis of platelet activating factor(PAF)in experimental hepatic cirrhosis,and to elucidate the effects of endothelin(ET)on portal hypertension.Methods Thirty SD rats were randomly assigned to two groups:control group and CCl4-induced hepatic cirrhotic group.Kupffer cells,isolated from the livers of animals in both groups,were cultured for 24h.ET-1-induced PAF synthesis,and mRNA expression of PAF,ET-1 receptor and preproendothelin-1 in Kupffer cells were determined by rapid 3H-PAF scintillation proximity assay,saturation binding technique and semi-quantitative reverse transcriptase polymerase chain reaction(RT-PCR),respectively.Results Cell-associated PAF synthesis and release increased about 1.48 folds and two-folds,respectively,by cirrhotic Kupffer cells as compared to the control(1.02 ? 0.06 vs 0.69 ? 0.07 pg /mg DNA in Kupffer cells and 1.42? 0.14 vs 0.66 ? 0.04 pg/mg DNA in medium).Endothelin-1 enhanced Kupffer cells to stimulate PAF synthesis in a concentration-dependent manner,and for cirrhotic Kupffer cells,the effect was more significant than control.Cirrhotic Kupffer cells also had increased densities of functional receptors for both PAF and ET-1(exclusively ETB),but did not change the affinity of these receptors.No mRNA transcripts for the ETA receptor or preproET-1 were detected.Conclusion Kupffer cell is the main source of PAF in the cirrhotic rats.ET-1 stimulates PAF synthesis in activated Kupffer cells via ETB receptor.Since both ET-1 and PAF individually cause portal hypertension,Kupffer cells may play a role in portal hypertension associated with liver cirrhosis.