Liver sinusoidal endothelial cell injury by neutrophils in rats with acute obstructive cholangitis.
OBJECTIVE
The objective of this study is to elucidate the potential role of poly-morphonuclear neutrophils (PMN) in the development of such a sinusoidal endothelial cell (SEC) injury during early acute obstructive cholangitis (AOC) in rats.


METHODS
Twenty one Wistar rats were divided into three groups: the AOC group, the bile duct ligated group (BDL group), and the sham operation group (SO group). The common bile duct (CBD) of rats in AOC group was dually ligated and 0.2 ml of the E. Coli O(111) B(4) (5 X 10(9)cfu/ml) suspension was injected into the upper segment, in BDL group, only the CBD was ligated and in SO group, neither injection of E. Coli suspension nor CBD ligation was done, but the same operative procedure. Such group consisted of seven rats, all animals were killed 6h after the operation. Morphological changes of the liver were observed under light and electron microscope. Expression of intercellular adhesion molecule-1 (ICAM-1) mRNA in hepatic tissue was determined with reverse transcription polymerase chain reaction (RT-PCR). The serum levels of alanine aminotransferase (ALT) were determined with an autoanalyger and cytokine-induced neutrophil chemoattractant (CINC) was determined by enzyme-linked immunosorbent assay (ELISA).


RESULTS
Neutrophils was accumulated in the hepatic sinusoids and sinusoidal endothelial cell injury existed in AOC group. In contrast, in rats of BDL group, all the features of SEC damage were greatly reduced. Expression of ICAM-1 mRNA in hepatic tissue in three groups were 7.54 +/- 0.82, 2.87 +/- 0.34, and 1.01 +/- 0.12, respectively. There were significant differences among three groups (P<0.05). The serum CINC levels in the three groups were 188 +/- 21 ng.L(-1), 94+/-11 ng.L(-1), and 57+/-8 ng.L(-1), respectively. There were also significant differences among the three groups (P<0.05). Activity of the serum ALT was 917 +/- 167 nkat.L(-1), 901 +/- 171 nkat.L(-1), and 908 +/- 164 nkat.L(-1), respectively, (P<0.05).


CONCLUSIONS
Hepatic SEC injury occurs earlier than hepatic parenchymal cells during AOC. Recruitments of circulating neutrophils in the hepatic sinusoidal space might mediate the SEC injury, and ICAM-1 in the liver may modulate the PMN of accumulation.
Gong
Jian-Ping
JP
Department of General Surgery, The Second College of Clinical Medicine & the Second Affiliated Hospital of Chongqing University of Medical Science, 74 Linjiang Road, Chongqing 400010, China. gongjianping11@hotmail.com
Wu
Chuan-Xin
CX
Liu
Chang-An
CA
Li
Sheng-Wei
SW
Shi
Yu-Jun
YJ
Li
Xu-Hong
XH
Peng
Yong
Y
D000208:Acute Disease; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D002761:Cholangitis / Q000473:pathology*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D009504:Neutrophils / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D018799:Intercellular Adhesion Molecule-1; D000410:Alanine Transaminase