Participation of the myeloperoxidase-H2O2-halide system in immune complex nephritis.
Neutrophils (PMNs) mediate injury in experimental glomerulonephritis (GN) in part via the release of reactive oxygen species, particularly hydrogen peroxide (H2O2). Recent kidney perfusion studies demonstrate that H2O2 can cause glomerular injury by reaction with halides in the presence of the PMN cationic enzyme myeloperoxidase (MPO) to form oxidants which can oxidize and halogenate tissue. We sought evidence for participation of the MPO system in a model of PMN-mediated immune complex (IC) GN. A PMN-dependent model of GN was developed in rats by perfusing the renal artery with concanavalin A followed by anticoncanavalin A antibody. PMN depletion abolished glomerular PMN infiltration and significantly reduced proteinuria (35 +/- 7 mg/day vs. 113 +/- 10, P less than 0.001). Rats that received Na125I (5.0 microCi) three and six hours following disease induction had more 125I incorporation in glomeruli and GBM at 48 hours than similarly treated rats that were PMN depleted (1200 cpm vs. 88 cpm, P less than 0.01). Glomerular iodination could not be demonstrated in a PMN-independent model of nephrotoxic nephritis induced with noncomplement fixing anti-GBM antibody. These data indicate that this model of PMN-mediated IC GN is associated with activation of the MPO-H2O2-halide system, which may participate in mediating glomerular injury.
Johnson
R J
RJ
Department of Medicine, University of Washington, Seattle.
Klebanoff
S J
SJ
Ochi
R F
RF
Adler
S
S
Baker
P
P
Sparks
L
L
Couser
W G
WG
D000818:Animals; D002196:Capillaries / Q000378:metabolism / Q000648:ultrastructure; D003176:Complement C3 / Q000032:analysis; D003208:Concanavalin A / Q000276:immunology; D005921:Glomerulonephritis / Q000209:etiology / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006219:Halogens / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007105:Immune Complex Diseases / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D007074:Immunoglobulin G; D007455:Iodine / Q000378:metabolism; D007678:Kidney Glomerulus / Q000098:blood supply / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D007958:Leukocyte Count; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D003176:Complement C3; D006219:Halogens; D007074:Immunoglobulin G; D003208:Concanavalin A; D007455:Iodine; D006861:Hydrogen Peroxide; D009195:Peroxidase