Table 1 |
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Summary of findings obtained using MPO-ANCA vasculitis animal models |
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|
Result |
Model |
Reference |
|
|
|
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|
Effector mechanisms |
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|
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 |
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|
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] |
|
|
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|
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]. |
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Heeringa and Little Arthritis Research & Therapy 2011 13:204 doi:10.1186/ar3236 |
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