Morphologic correlates of glomerular oxidant injury induced by the myeloperoxidase-hydrogen peroxide-halide system of the neutrophil.
Neutrophilic polymorphonuclear leukocytes can mediate glomerulonephritis by releasing reactive oxygen species such as H2O2. We have previously demonstrated that H2O2-mediated glomerular injury can be potentiated by reaction with polymorphonuclear leukocyte myeloperoxidase (MPO). When MPO was perfused into renal arteries of rats, it bound to the glomerular capillary wall due to its cationic charge. Subsequent perfusion with nontoxic concentrations of H2O2 and halides resulted in acute glomerular injury, halogenation of the glomerular basement membrane, and proteinuria. The studies reported here document the morphologic changes that accompany MPO-mediated glomerular injury. Acutely, there is severe injury to the endothelium with cell swelling and lysis. Within 10 minutes, a marked platelet influx occurs. Platelets frequently occlude capillary lumens and bind to areas of denuded glomerular basement membrane where platelet degranulation results. By 4 days, the platelet infiltration has ceased, and a reparative phase develops characterized by marked proliferation of resident endothelial cells and possibly mesangial cells. By 21 days postperfusion, the glomerular lesion had largely resolved. In contrast, control rats perfused with MPO alone, H2O2 alone, or buffered saline alone demonstrate minimal glomerular injury at all times studied. MPO-mediated glomerular disease results in endothelial and mesangial cell injury, activation of platelets, and a subsequent proliferative response. These morphologic changes resemble those seen in several forms of inflammatory and proliferative glomerulonephritis in man.
Johnson
R J
RJ
Department of Medicine, University of Washington, Seattle.
Guggenheim
S J
SJ
Klebanoff
S J
SJ
Ochi
R F
RF
Wass
A
A
Baker
P
P
Schulze
M
M
Couser
W G
WG
D000818:Animals; D005921:Glomerulonephritis / Q000378:metabolism / Q000473:pathology*; D006219:Halogens / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000473:pathology* / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D009504:Neutrophils / Q000201:enzymology / Q000378:metabolism*; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000378:metabolism*; D011507:Proteinuria; D051381:Rats; D011919:Rats, Inbred Strains
D006219:Halogens; D006861:Hydrogen Peroxide; D009195:Peroxidase