A specific Thy-1 molecular epitope expressed on rat mesangial cells

Exp Nephrol. Nov-Dec 1996;4(6):350-60.

Abstract

An experimental model of proliferative glomerulonephritis induced by antibodies against the Thy-1 antigen has been established and used to study the pathological sequence from mesangiolysis to mesangial proliferation. However, the functional role of the Thy-1 molecule distributed on rat glomerular mesangial cells remains unknown, so the present study was undertaken to determine the precise subcellular localization of Thy-1 molecules in vitro using two anti-Thy-1 monoclonal antibodies, 1-22-3 and OX-7. Immunofluorescence and immunoelectron microscopic studies in combination with laser scanning analysis showed that the localization of 1-22-3 and OX-7 bound to cultured rat mesangial cells differed, particularly when cocultured with vascular endothelial cells. An epitope recognized by 1-22-3 was concentrated specifically on the mesangial cell surfaces facing the neighboring endothelial cells. In contrast, OX-7 bound to mesangial cell surfaces and extracellular parts in a diffuse pattern independent of contact with endothelial cells. This finding is consistent with our previous ultrastructural study in which the reactivity of 1-22-3 with normal kidney tissue was limited to mesangial cell surfaces facing endothelial cells. These results led us to conclude that the specific Thy-1 molecular epitope recognized by 1-22-3 is associated with points anchoring mesangial and endothelial cells, where this anti-Thy-1 antibody binds after injection in vivo, resulting in mesangial cell detachment from the vascular capillary wall, mesangiolysis and mesangial cell dysfunction. We believe that the critical epitope detected by 1-22-3 in this study plays an important role in mesangial cell function and injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • Cell Communication
  • Cells, Cultured
  • Disease Models, Animal
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / immunology
  • Epitopes / metabolism
  • Glomerular Mesangium / cytology
  • Glomerular Mesangium / immunology*
  • Glomerulonephritis, Membranoproliferative / etiology
  • Glomerulonephritis, Membranoproliferative / immunology
  • Immunohistochemistry
  • Microscopy, Confocal
  • Microscopy, Electron
  • Microscopy, Fluorescence
  • Rats
  • Subcellular Fractions / immunology
  • Thy-1 Antigens / metabolism*

Substances

  • Antibodies, Monoclonal
  • Epitopes
  • Thy-1 Antigens