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].

Heeringa and Little Arthritis Research & Therapy 2011 13:204   doi:10.1186/ar3236