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Updated: Aug 24, 2026
Detecting Migration and Infiltration of Neutrophils in Mice
Published on: February 6, 2020
Neutrophil contribution to the crescentic glomerulonephritis in SCG/Kj mice
Akiko Ishida-Okawara1, Toshiko Ito-Ihara, Eri Muso
1Biodefense Laboratory, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo, 162-8640, Japan.
Background:
Myeloperoxidase-specific anti-neutrophil cytoplasmic auto-antibody (MPO-ANCA) has been a useful diagnostic marker in systemic vasculitis with crescentic glomerulonephritis (CrGN). It is highly suspected that the antigenic enzyme MPO released from activated neutrophils is involved in these lesions. We evaluated the relationship between neutrophil functions including peripheral neutrophil counts and renal lesions in SCG/Kj mice as a model of ANCA-associated CrGN and vasculitis.
Methods:
Peripheral neutrophil counts, the plasma levels of MPO-ANCA and tumour necrosis factor alpha (TNF-alpha) were measured. The capacity of MPO release and superoxide generation were evaluated as neutrophil activity. The renal lesions were estimated by grade of proteinuria, histopathological lesion, such as glomerular neutrophil infiltration and active or chronic renal injury scores with crescent formation.
Results:
MPO-ANCA and TNF-alpha levels were higher than those of normal mice C57BL/6 even before overt proteinuria; subsequently, peripheral neutrophils increased. In the phase of nephritis with low grade proteinuria, the spontaneous release of MPO from peripheral neutrophils increased, while superoxide generation increased before spontaneous MPO release occurred. In addition, the renal lesion in histological observations was aggravated with ageing and the glomerular neutrophil infiltration was positively correlated with MPO-ANCA levels, as well as with histological indices of nephritis, active renal injury score; in particular, crescent formation was correlated with spontaneous MPO release. In contrast, superoxide generation was negatively correlated with the severity of this lesion during the progression.
Conclusions:
These findings indicate that neutrophils are activated and contribute to the development of the active crescentic lesion in SCG/Kj mice.
Insights
Neutrophil activation and myeloperoxidase (MPO) release are key factors in the development of ANCA-associated glomerulonephritis in mice. Increased MPO-ANCA levels correlate with kidney damage and crescent formation.
Area of Science:
- Nephrology
- Immunology
- Pathology
Background:
- Myeloperoxidase-specific anti-neutrophil cytoplasmic auto-antibody (MPO-ANCA) is a diagnostic marker for systemic vasculitis with crescentic glomerulonephritis (CrGN).
- Activated neutrophils and their released MPO are suspected contributors to CrGN lesions.
Purpose of the Study:
- To investigate the relationship between neutrophil functions and renal lesions in a mouse model of ANCA-associated CrGN and vasculitis.
Main Methods:
- Measured peripheral neutrophil counts, MPO-ANCA, and TNF-alpha levels.
- Assessed neutrophil MPO release and superoxide generation.
- Evaluated renal lesions including proteinuria, glomerular neutrophil infiltration, and active/chronic renal injury scores with crescent formation.
Main Results:
- Elevated MPO-ANCA and TNF-alpha preceded proteinuria; peripheral neutrophils increased thereafter.
- Spontaneous MPO release and superoxide generation by neutrophils increased during nephritis.
- Glomerular neutrophil infiltration correlated with MPO-ANCA levels and nephritis severity, particularly crescent formation.
Conclusions:
- Neutrophil activation and MPO release contribute to active crescentic lesions in this mouse model.
- Findings support the role of neutrophils in ANCA-associated glomerulonephritis pathogenesis.
