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

• 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
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1007/s10620-009-0785-5

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.