Table 1.
Summary of findings obtained using MPO-ANCA vasculitis animal models
| Result | Model | Reference | |
|---|---|---|---|
| Effector mechanisms | |||
| Neutrophil | Neutrophil depletion abrogates crescentic glomerulonephritis. | Mouse | [24] |
| T cells | CD4+ effector T cells contribute to anti-MPO-mediated crescentic glomeruloneprhitis. | Mouse (anti-GBM) | [55] |
| Th17 cells promote anti-MPO-mediated crescentic glomerulonephritis. | Mouse (anti-GBM) | [56] | |
| Proinflammatory stimuli | Lipopolysaccharide aggravates crescentic glomerulonephritis in a TLR4-dependent manner. | Mouse | [25] |
| Pertussis toxin/Mycobacterium tuberculosis aggravates crescentic glomerulonephritis. | Rat | [59] | |
| IgG glycosylation | IgG glycan hydrolysis attenuates crescentic glomeruloneprhitis. | Mouse | [38] |
| Leukocyte-endothelial interactions | Anti-MPO IgG increases leukocyte adhesion and migration in cremasteric venules. | Rat | [20] |
| Anti-MPO IgG increases leukocyte adhesion in glomerular capillaries. | Mouse | [27] | |
| Genetic susceptibility | Rat and mouse strains differ in susceptibility to anti-MPO-mediated crescentic glomerulonephritis. | Rat | [59] |
| Mouse | [21] | ||
| Targets for treatment | |||
| Complement pathway | Disruption of alternative complement pathway abrogates crescentic glomerulonephritis. | Mouse | [29] |
| Genetic ablation of C5aR attenuates crescentic glomerulonephritis. | Mouse (BM) | [30] | |
| PI3Kγ signalling | Genetic ablation of PI3Kγ attenuates crescentic glomerulonephritis. | Mouse (BM) | [33] |
| Experimental therapies | |||
| Anti-TNFα treatment | Anti-TNFα pretreatment attenuates crescentic glomerulonephritis. | Rat | [32] |
| Mouse | [25] | ||
| Anti-C5 treatment | Anti-C5 pretreatment abrogates and treatment attenuates crescentic glomerulonephritis. | Mouse | [31] |
| PI3Kγ inhibitor treatment | Treatment with a PI3Kγ inhibitor attenuates crescentic glomerulonephritis. | Mouse (BM) | [33] |
| P38 MAPK inhibitor treatment | Treatment with a P38 MAPK inhibitor attenuates crescentic glomerulonephritis. | Mouse | [36] |
anti-GBM refers to the mouse model in which low-dose anti-glomerular basement membrane administration triggers disease in myeloperoxidase-immunized mice. BM refers to the bone marrow transplantation myeloperoxidase-anti-neutrophil cytoplasm autoantibody (MPO-ANCA) mouse model. C5aR, C5a receptor; MAPK, mitogen-activated protein kinase; PI3Kγ, phosphatidylinositol 3 kinase-gamma; Th17, T helper 17; TLR4, Toll-like receptor 4; TNFα, tumor necrosis factor-alpha. Adapted from [23].