Redistribution of glomerular dipeptidyl peptidase type IV in experimental lupus nephritis. Demonstration of decreased enzyme activity at the ultrastructural level.
BACKGROUND
In murine chronic graft-versus-host disease, an experimental model for lupus nephritis, autoantibodies against renal tubular epithelium can be found. Part of these antibodies are directed against a constituent of renal tubular epithelium, the enzyme Dipeptidyl peptidase IV (DPP IV). DPP IV is present on the cell membrane of glomerular epithelial and endothelial cells, and plays an important role in cell-extracellular matrix interactions. In mice and rats, administration of heterologous anti-DPP IV antibodies can induce proteinuria and podocyte effacement.


METHODS
In this study, the glomerular DPP IV enzyme activity was investigated in the course of graft-versus-host disease in (C57BL/10 x DBA/2) F1 hybrids both by light- and electron microscopy using a DPP IV-specific substratum.


RESULTS
Light microscopical examination revealed an overall reduction of DPP IV activity and an altered distribution pattern in glomeruli as early as 4 weeks after induction of graft-versus-host disease. Immunofluorescence studies using anti-DPP IV antibodies showed actual redistribution, excluding antibody-mediated enzyme inactivation. Enzyme electron microscopy revealed an irregular deposition of reaction product characterized by a patchy, "moth eaten" appearance of the endothelial and epithelial membranes. This process occurred simultaneously with the development of albuminuria and preceded the effacement of epithelial foot processes. In control mice, DPP IV showed a continuous distribution along endothelial and podocyte membranes.


CONCLUSIONS
In view of these findings we postulate that impairment of the function of DPP IV as a non integrin adhesion molecule may be one of the causative factors underlying the structural and functional lesions observed in this model for lupus nephritis.
van Leer
E H
EH
Department of Pathology, University of Leiden, The Netherlands.
Bruijn
J A
JA
Prins
F A
FA
Hoedemaeker
P J
PJ
de Heer
E
E
D000419:Albuminuria / Q000209:etiology; D000818:Animals; D015153:Blotting, Western; D002462:Cell Membrane / Q000201:enzymology / Q000648:ultrastructure; D018819:Dipeptidyl Peptidase 4; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000032:analysis* / Q000097:blood / Q000235:genetics; D004195:Disease Models, Animal; D004727:Endothelium / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure; D004789:Enzyme Activation; D004848:Epithelium / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure; D005260:Female; D005455:Fluorescent Antibody Technique; D006086:Graft vs Host Disease / Q000201:enzymology / Q000473:pathology; D007678:Kidney Glomerulus / Q000201:enzymology* / Q000473:pathology / Q000648:ultrastructure; D008181:Lupus Nephritis / Q000201:enzymology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008854:Microscopy, Electron
D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D018819:Dipeptidyl Peptidase 4