Open AccessReactive oxygen species and neutrophil respiratory burst cytochrome b558 are produced by kidney glomerular cells in passive Heymann nephritis.
Author(s) -
T. J. Neale,
Robert C. Ullrich,
P P Ojha,
Helga Poczewski,
Arthur J. Verhoeven,
Dontscho Kerjaschki
Publication year - 1993
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.90.8.3645
Subject(s) - immunoelectron microscopy , glomerulonephritis , microbiology and biotechnology , respiratory burst , glomerular basement membrane , biology , chemistry , proteinuria , cytochrome , pathology , kidney , immunohistochemistry , immunology , endocrinology , biochemistry , medicine , enzyme
Reactive oxygen species (ROS) have been implicated in the production of glomerular damage in passive Heymann nephritis (PHN), an experimental form of membranous nephropathy with neutrophil-independent proteinuria. Immunohistochemistry with monoclonal antibodies specific for cytochrome b558 (a major component of the oxidoreductase complex of the respiratory burst in stimulated neutrophilic granulocytes) showed that this enzyme is localized within visceral glomerular epithelial cells (GECs) in a dense, granular pattern in rats with PHN and proteinuria. By immunoelectron-microscopy, the cytochrome was found in membrane vesicles within the GEC and also extracellularly on the GEC membranes facing the glomerular basement membrane (GBM). By immunoblotting, cytochrome b558 was detected in highest concentration in lysates of isolated glomeruli from proteinuric rats. By contrast, only traces were found in normal glomeruli by immunohistochemistry. Depletion of complement abolished the expression of the cytochrome. Using an ultrastructural cerium-H2O2 histochemistry technique, the functional activity of the glomerular ROS-generating system was demonstrated exclusively in proteinuric PHN, where H2O2 was found in highest concentration within the GBM. These results provide evidence that in rats with PHN and proteinuria, the GECs express and externalize respiratory-burst enzymes that generate ROS in a manner similar to neutrophilic granulocytes, which could then lead to glomerular damage.