title: Liver endothelial cells promote LDL-R expression and the uptake of HCV-like particles in primary rat and human hepatocytes.
abstract: Low-density lipoprotein (LDL) is an important carrier of plasma cholesterol and triglycerides whose concentration is regulated by the liver parenchymal cells. Abnormal LDL regulation is thought to cause atherosclerosis, while viral binding to LDL has been suggested to facilitate hepatitis C infection. Primary hepatocytes quickly lose the ability to clear LDL during in vitro culture. Here we show that the coculture of hepatocytes with liver sinusoidal endothelial cells (LSEC) significantly increases the ability of hepatocytes to uptake LDL in vitro. LDL uptake does not increase when hepatocytes are cocultured with other cell types such as fibroblasts or umbilical vein endothelial cells. We find that LSECs induce the hepatic expression of the LDL receptor and the epidermal growth factor receptor. In addition, while hepatocytes in single culture did not take up hepatitis C virus (HCV)-like particles, the hepatocytes cocultured with LSECs showed a high level of HCV-like particle uptake. We suggest that coculture with LSECs induces the emergence of a sinusoidal surface in primary hepatocytes conducive to the uptake of HCV-like particles. In conclusion, our findings describe a novel model of polarized hepatocytes in vitro that can be used for the study of LDL metabolism and hepatitis C infection.
authors.affiliation: Center for Engineering in Medicine/Department of Surgery, Massachusetts General Hospital, Shriners Burns Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Yaakov
authors.initials: Y
authors.lastname: Nahmias
authors.forename: Monica
authors.initials: M
authors.lastname: Casali
authors.forename: Laurent
authors.initials: L
authors.lastname: Barbe
authors.forename: Francois
authors.initials: F
authors.lastname: Berthiaume
authors.forename: Martin L
authors.initials: ML
authors.lastname: Yarmush
mesh_terms: D000818:Animals; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000502:physiology*; D066246:ErbB Receptors / Q000096:biosynthesis; D005260:Female; D000077614:Golgi Matrix Proteins; D016174:Hepacivirus; D017228:Hepatocyte Growth Factor / Q000502:physiology; D022781:Hepatocytes / Q000378:metabolism* / Q000821:virology*; D006801:Humans; D008099:Liver / Q000166:cytology*; D008565:Membrane Proteins; D051381:Rats; D011973:Receptors, LDL / Q000096:biosynthesis*; D011991:Receptors, Virus / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D033921:Vesicular Transport Proteins; D014771:Virion / Q000502:physiology
chemical_list: D000077614:Golgi Matrix Proteins; D008565:Membrane Proteins; D011973:Receptors, LDL; D011991:Receptors, Virus; D014409:Tumor Necrosis Factor-alpha; D033921:Vesicular Transport Proteins; C091580:vesicular transport factor p115; D017228:Hepatocyte Growth Factor; D066246:ErbB Receptors