Antigenic specificities of glomerular-bound autoantibodies in membranous glomerulopathy induced by mercuric chloride.
The present study describes the development of membranous glomerulopathy (MGP) with high proteinuria in DZB rats exposed to mercuric chloride (HgCl2). IgG1 and IgG2a antibodies, eluted from glomeruli with subepithelial immune deposits, bind to the interface of the GBM and epithelial cells. High reactivity to GBM was demonstrated by ELISA and Western blotting, which could be absorbed for 30% by laminin or laminin-associated extracellular matrix components. No reactivity was found with type IV collagen, fibronectin, heparan sulfate proteoglycans, or tubular brush border antigens. Absorption to GBM removed the reactivity to renal antigens. Passively transferred eluted antibodies bind in a predominantly linear pattern along the GBM, causing focal ultrastructural transformations of the podocytes. These results suggest that this type of HgCl2-induced MGP, associated with epithelial cell injury and proteinuria, is caused by autoantibodies to basement membrane components which are located at the epithelial cell-basement membrane interface and may be involved in cell-matrix binding.
Aten
J
J
Department of Pathology, University of Leiden, The Netherlands.
Veninga
A
A
Bruijn
J A
JA
Prins
F A
FA
de Heer
E
E
Weening
J J
JJ
D000818:Animals; D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology*; D015153:Blotting, Western; D003094:Collagen / Q000276:immunology; D003176:Complement C3 / Q000096:biosynthesis; D003186:Complement C9 / Q000096:biosynthesis; D015938:Complement Membrane Attack Complex / Q000096:biosynthesis; D003429:Cross Reactions; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005353:Fibronectins / Q000276:immunology; D015433:Glomerulonephritis, Membranous / Q000139:chemically induced / Q000276:immunology*; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate / Q000276:immunology; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000276:immunology; D007797:Laminin / Q000276:immunology; D008627:Mercuric Chloride; D008854:Microscopy, Electron; D011507:Proteinuria / Q000139:chemically induced; D011509:Proteoglycans / Q000276:immunology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D001323:Autoantibodies; D003094:Collagen; D003176:Complement C3; D003186:Complement C9; D015938:Complement Membrane Attack Complex; D005353:Fibronectins; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D007073:Immunoglobulin E; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007797:Laminin; D008627:Mercuric Chloride; D011509:Proteoglycans