A specific Thy-1 molecular epitope expressed on rat mesangial cells.
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.
Oite
T
T
Department of Immunology, Niigata University School of Medicine, Japan.
Saito
M
M
Suzuki
Y
Y
Arii
T
T
Morioka
T
T
Shimizu
F
F
D000818:Animals; D000911:Antibodies, Monoclonal; D002450:Cell Communication; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology; D000939:Epitopes / Q000378:metabolism; D005920:Glomerular Mesangium / Q000166:cytology / Q000276:immunology*; D015432:Glomerulonephritis, Membranoproliferative / Q000209:etiology / Q000276:immunology; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D051381:Rats; D013347:Subcellular Fractions / Q000276:immunology; D018800:Thy-1 Antigens / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000939:Epitopes; D018800:Thy-1 Antigens