NDT Advance Access originally published online on May 18, 2004
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Nephrol Dial Transplant (2004) 19: 1708-1715
Nephrol Dial Transplant Vol. 19 No. 7 © ERA-EDTA 2004; all rights reserved
Original Article
Neutrophil contribution to the crescentic glomerulonephritis in SCG/Kj mice
1 Biodefense Laboratory, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan, 2 Nephrology Division, Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kawara-cho 54, Shogoin, Sakyou-ku, Kyoto 606-8507, Japan, 3 Division of Nephrology and Dialysis, Kitano Hospital, The Tazuke Kofukai Medical Research Institute, 2-4-20 Ohgimachi, Kita-ku, Osaka 530-8480, Japan and 4 Nippon Kayaku Co. Ltd, 31-12, Shimo, 3-chome, Kita-ku 115-8588, Japan
Correspondence and offprint requests to: Kazuo Suzuki, PhD, Chief of Biodefense Laboratory, National Institute of Infectious Diseases (NIID-NIH), Toyama 1-23-1, Shinjuku-ku, Tokyo, 162-8640, Japan. Email: ksuzuki{at}nih.go.jp. The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.
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-
) 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- 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.
Keywords: activated neutrophils; crescentic glomerulonephritis; MPO-ANCA; SCG/Kj mice; TNF-
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