Fig. 4.

MPO_409–428 immunization induces nephritogenic autoimmunity. C57BL/6 mice were immunized with either OVA_323–339 [control (n = 5), □], MPO_409–428 (n = 6, ●), or native mouse MPO (n = 4, ○), and disease was triggered by recruiting neutrophils to glomeruli with low-dose sheep anti-mouse GBM Ab. Mice immunized with an irrelevant antigen (OVA_323–339) and injected with low-dose sheep anti-mouse GBM Ab developed minimal injury, whereas mice immunized with MPO_409–428 developed FNGN similar to that induced by immunization with whole-mouse MPO. Functional indices of glomerular injury, albuminuria (A) and blood urea nitrogen (B), were increased after MPO-specific immunization. Some glomeruli from MPO_409–428- and whole MPO–immunized mice exhibited segmental necrosis (H&E) (C and E–G) with glomerular fibrin deposition (fibrin as the brown reaction product) (D and H–J). Photomicrographs of glomeruli and fibrin deposition are taken at a magnification of 400×. (Scale bars: E–J, 10 μm.) Glomerular infiltrates of CD4⁺ T cells (K) and macrophages (L) but not neutrophils (M) were increased after MPO_409–428 immunization. gcs, glomerular cross section. *P < 0.05; **P < 0.01; ***P < 0.001.