Alterations of Bone Marrow Sinusoidal Endothelium in Rat and Patients with Liver Cirrhosis

Whether bone marrow changes occur and potentially contribute to the hematological abnormalities in liver cirrhosis remain unclear. In this study, we established a rat model of liver cirrhosis induced by carbon tetrachloride. Electron microscopy examination showed focal lesions in bone marrow sinusoi...

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Bibliographic Details
Published in:Digestive diseases and sciences 2010-03, Vol.55 (3), p.654-661
Main Authors: Zhao, Song, Fu, Ying-Mei, Li, Xiu-Fen, Jin, Zhan-Feng, Zhao, Rui-Bo, Huang, Qi, Zhang, Feng-Min, Zhang, Wei-Hui
Format: Article
Language:English
Subjects:
Animals
Biochemistry
Biological and medical sciences
Bone Marrow - chemistry
Bone Marrow - pathology
Bone Marrow - physiopathology
Bone Marrow Cells - pathology
Carbon tetrachloride
Carbon Tetrachloride Poisoning - pathology
DNA polymerases
E-Selectin - analysis
Endothelial Cells - pathology
Endothelial Cells - physiology
Endothelium
Feeding. Feeding behavior
Fundamental and applied biological sciences. Psychology
Gastroenterology
Gastroenterology. Liver. Pancreas. Abdomen
Hepatology
Humans
Immunohistochemistry
Liver cirrhosis
Liver Cirrhosis - pathology
Liver Cirrhosis - physiopathology
Liver. Biliary tract. Portal circulation. Exocrine pancreas
Medical research
Medical sciences
Medicine
Medicine & Public Health
Medicine, Experimental
Methylene blue
Microscopy, Electron
Oncology
Original Article
Other diseases. Semiology
P-Selectin - analysis
Rats
Rats, Wistar
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - analysis
Transplant Surgery
Vertebrates: anatomy and physiology, studies on body, several organs or systems
von Willebrand Factor - analysis
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Summary:Whether bone marrow changes occur and potentially contribute to the hematological abnormalities in liver cirrhosis remain unclear. In this study, we established a rat model of liver cirrhosis induced by carbon tetrachloride. Electron microscopy examination showed focal lesions in bone marrow sinusoidal endothelium and hematopoietic cells in animals with cirrhosis. With the persistence of liver cirrhosis, injuries of bone marrow sinusoidal endothelium progressed from mild mitochondrial changes to nuclear pycnosis and cell disruption, and the trilineage hematopoietic cells showed apoptosis and necrosis. Immunohistochemistry revealed increased expression of E-selectin, P-selectin and vWF in bone marrow sinusoidal endothelium of the cirrhotic rats, which was consistent with the data from semiquantitative reverse transcriptase-polymerase chain reaction analysis. Autopsy specimens from patients with liver cirrhosis (in the absence of other disease) showed the same findings as detected by immunohistochemistry in animal models. The results provide evidence of the association between liver cirrhosis and bone marrow alterations by demonstrating the bone marrow sinusoidal endothelium lesions in both a rat model and patients. It also indicates that activation or injury of bone marrow sinusoidal endothelium mediated by E-selectin, P-selectin, and vWF might have a role in pathogenesis of bone marrow changes during liver cirrhosis. The lesions of bone marrow sinusoidal endothelium might contribute to the hematological abnormalities in the end stage of liver disease.
ISSN:0163-2116
1573-2568
DOI:10.1007/s10620-009-0785-5