Hepatocytes may produce laminin in fibrotic liver and in primary culture

Authors

  • Bruno Clément M.D.,

    Corresponding author
    1. Unité de Recherches Hépatologiques U 49 de l'INSERM, Hǒpital de Pontchaillou, 35033 Rennes, France
    • Unité de Recherches Hépatologiques U 49 de l'INSERM, Hǒpital de Pontchaillou, 35033 Rennes Cédex, France
    Search for more papers by this author
  • Pierre-Yves Rescan,

    1. Unité de Recherches Hépatologiques U 49 de l'INSERM, Hǒpital de Pontchaillou, 35033 Rennes, France
    Search for more papers by this author
    • “La Ligue Nationale Française contre le Cancer,” and O. Loréal was a recipient of a fellowship from “La Fondation pour la Recherche Médicale Française.”

  • Georges Baffet,

    1. Unité de Recherches Hépatologiques U 49 de l'INSERM, Hǒpital de Pontchaillou, 35033 Rennes, France
    Search for more papers by this author
  • Olivier Loréal,

    1. Unité de Recherches Hépatologiques U 49 de l'INSERM, Hǒpital de Pontchaillou, 35033 Rennes, France
    Search for more papers by this author
  • Dominique Lehry,

    1. Unité de Recherches Hépatologiques U 49 de l'INSERM, Hǒpital de Pontchaillou, 35033 Rennes, France
    Search for more papers by this author
  • Jean-Pierre Campion,

    1. Unité de Recherches Hépatologiques U 49 de l'INSERM, Hǒpital de Pontchaillou, 35033 Rennes, France
    Search for more papers by this author
  • André Guillouzo

    1. Unité de Recherches Hépatologiques U 49 de l'INSERM, Hǒpital de Pontchaillou, 35033 Rennes, France
    Search for more papers by this author

Abstract

Previous studies have shown that laminin is present in basement membranes in normal liver but failed to identify cellular sources. We have investigated the extracellular and intracellular distribution of laminin in normal rat and human liver, in fibrotic human liver and in primary hepatocyte cultures from both species by light and electron microscopy using the indirect immunoperoxidase technique. In normal liver from both species, antibodies to laminin strongly stained basement membranes and formed discontinuous discrete deposits in the wall of the sinusoid. Vascular endothelial and bile duct cells as well as fat-storing cells and sinusoidal endothelial cells strongly stained for this glycoprotein while hepatocytes were negative. In fibrotic human liver, increased amounts of extracellular laminin were usually found. Continuous deposition in the space of Disse was observed in some cases. In addition to fat-storing cells and endothelial cells, hepatocytes were also sometimes positive. Normal rat and human hepatocytes synthesize and secrete laminin in conventional culture, but it remains soluble in the medium. By contrast, in coculture with another rat liver cell type, laminin accumulated around hepatocyte cords. These observations suggest that fat-storing cells and endothelial cells are the major sites of production of laminin in normal liver. However, when their environment is altered (e.g., liver injury, culture), adult hepatocytes are able to synthesize detectable amounts of laminin.

Ancillary