title: Expression of LYVE-1 in sinusoidal endothelium is reduced in chronically inflamed human livers.
abstract: BACKGROUND
  LYVE-1, a specific marker of lymphatics, is expressed in hepatic sinusoidal endothelium. A previous study revealed that LYVE-1 expression in sinusoidal endothelium was reduced in cirrhosis. However, it is still obscure how LYVE-1 expression in sinusoidal endothelium was reduced during the disease progression. To elucidate whether there were relationships among LYVE-1 attenuation, sinusoidal capillarization, and disease progression, we performed immunohistochemical investigations based on frozen human livers.
  
  
  METHODS
  Frozen liver sections of chronic hepatitis (n = 8), cirrhosis (n = 13), and normal/control liver (n = 10) were examined by immunostaining for lymphatic endothelial markers (LYVE-1 and D2-40) and vascular endothelial markers (CD31 and von Willebrand factor). Computer-aided morphometry was applied to obtain objective data. The diseased liver tissues were also examined ultrastructurally.
  
  
  RESULTS
  In controls, sinusoidal endothelium was positive for LYVE-1 and CD31, but negative for D2-40 and von Willebrand factor. In chronic hepatitis and cirrhosis, LYVE-1 expression in sinusoidal endothelium was attenuated, especially in areas adjacent to active inflammatory or fibrotic lesions, while von Willebrand factor was reciprocally expressed in sinusoidal endothelium. The morphometric analyses revealed that LYVE-1 positivity in sinusoidal endothelium was significantly (P < 0.0001) decreased in chronic hepatitis and cirrhosis compared to controls and was negatively correlated (Rs = -0.72, P < 0.0001) to von Willebrand factor positivity. Furthermore, LYVE-1 positivity was negatively correlated to inflammatory grade (Rs = -0.51, P = 0.021) and fibrosis severity (Rs = -0.46, P = 0.038). Sinusoidal endothelium in the diseased livers showing LYVE-1 attenuation had lost fenestrations.
  
  
  CONCLUSIONS
  These findings indicated that LYVE-1 attenuation in sinusoidal endothelium was one of the manifestations of capillarization, and was associated with hepatic disease progression.
authors.affiliation: Department of Pathology, Osaka City University Graduate School of Medicine, 1-4-3, Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Arimoto
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ikura
authors.forename: Takehisa
authors.initials: T
authors.lastname: Suekane
authors.forename: Masashi
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Chizuko
authors.initials: C
authors.lastname: Kitabayashi
authors.forename: Yoko
authors.initials: Y
authors.lastname: Iwasa
authors.forename: Kenichi
authors.initials: K
authors.lastname: Sugioka
authors.forename: Takahiko
authors.initials: T
authors.lastname: Naruko
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Arakawa
authors.forename: Makiko
authors.initials: M
authors.lastname: Ueda
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D002196:Capillaries / Q000378:metabolism; D015925:Cryopreservation; D003936:Diagnosis, Computer-Assisted; D018450:Disease Progression; D004729:Endothelium, Lymphatic / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006521:Hepatitis, Chronic / Q000473:pathology*; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D012720:Severity of Illness Index; D033921:Vesicular Transport Proteins / Q000235:genetics* / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; C119248:LYVE1 protein, human; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D033921:Vesicular Transport Proteins; C500987:monoclonal antibody D2-40; D014841:von Willebrand Factor