Renal ischemia/reperfusion injury contributes to renal damage in experimental anti-myeloperoxidase-associated proliferative glomerulonephritis.
The occurrence of focal fibrinoid necrosis of capillary loops in the very early stages of ANCA-associated necrotizing crescentic glomerulonephritis (NCGN) and the increased prevalence of this disease at older age suggest that renal ischemia may play an additional role in its pathophysiology. In the present study we investigated the contribution of renal ischemia to the induction of anti-myeloperoxidase (MPO) associated NCGN in a previously described rat model of this disease. The development of renal lesions is dependent on the presence of an anti-MPO immune response and the localization of a lysosomal extract containing lytic enzymes and MPO in combination with hydrogen peroxide (H2O2) along the glomerular basement membrane (GBM). The hypothesis tested whether perfusion of hydrogen peroxide (H2O2) could be replaced by ischemia/reperfusion (I/R) injury, as I/R injury activates endothelial cells to produce oxygen metabolites. I/R was induced by clamping the renal artery for 20 minutes in kidneys in which the circulation had been restored several minutes after perfusion with the lysosomal extract in MPO immunized rats. Rats developed lesions characterized by intra- and extracapillary cell proliferation, periglomerular infiltration, ruptures in Bowman's capsule, ischemic tubuli, and interstitial mononuclear infiltrate. Immune deposits, however, persisted for a longer time along the GBM after perfusion of lytic enzymes followed by I/R injury compared to previous studies in which H2O2 in conjunction with lytic enzymes were perfused in MPO-immunized rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Brouwer
E
E
Department of Clinical Immunology and Pathology, University of Groningen, The Netherlands.
Klok
P A
PA
Huitema
M G
MG
Weening
J J
JJ
Kallenberg
C G
CG
D000818:Animals; D003176:Complement C3 / Q000378:metabolism*; D015432:Glomerulonephritis, Membranoproliferative / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism*; D016130:Immunophenotyping; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D009195:Peroxidase / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D015427:Reperfusion Injury / Q000150:complications* / Q000378:metabolism; D000267:Tissue Adhesions; D015854:Up-Regulation
D003176:Complement C3; D007074:Immunoglobulin G; D018799:Intercellular Adhesion Molecule-1; D009195:Peroxidase