Antibody induced injury to podocytes with proteinuria and foot process swelling in a transgenic (T16) mouse.
T16 mice contain a human 3' untranslated sequence of the Thy 1.1 gene. Unlike normal mice they express Thy 1.1 protein on the podocytes which was immuno-localized to podocyte apical and basal plasma membranes and filtration slit. When monoclonal anti-Thy 1.1 antibody (OX7) was injected in nonproteinuric heterozygous mice there was rapid podocyte foot process swelling and proteinuria. Immunofluorescence showed granular glomerular OX7 binding at one hour. Progressive loss of pedicels occurred with 17.9 +/- 2.5, 14.4 +/- 1.1 and 10.5 +/- 3.5 per 10 nm glomerular basement membrane (GBM) remaining 1, 6 and 24 hours, respectively, after 1 mg OX7, vs 32.2 +/- 2.0 in T16 mice given saline. Twenty-four hour proteinuria was OX7 dose-dependent, peaked at 1-3 days and reduced to near basal levels 9-11 days thereafter. Proteinuria was nonselective except at very low doses (0.1 mg OX7) where microalbuminuria was seen. F(ab')2 OX7 administration also caused proteinuria in T16 mice. One milligram F(ab')1 OX7 caused diffuse foot process swelling without manifest proteinuria in T16 mice. Anti-Thy 1.1 IgM monoclonal antibody did not produce the effects of OX7 in T16 mice. Foot process swelling was not modified by histamine or 5-hydroxytryptamine antagonists. OX7 did not cause complement activation or leucocyte infiltration, hence glomerular injury appeared to be mediated directly by the antibody.
Ebrahim
H
H
Department of Histopathology, Imperial College School of Medicine at St. Mary's, London, UK.
Evans
D J
DJ
D000419:Albuminuria / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D005455:Fluorescent Antibody Technique; D007518:Isoantibodies / Q000276:immunology*; D007678:Kidney Glomerulus / Q000276:immunology* / Q000648:ultrastructure; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D011507:Proteinuria / Q000276:immunology* / Q000473:pathology
D000911:Antibodies, Monoclonal; D007518:Isoantibodies; C035678:anti-Thy antibody