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Trafficking of QD‐Conjugated MPO‐ANCA in Murine Systemic Vasculitis and Glomerulonephritis Model Mice
Author(s) -
Hoshino Akiyoshi,
Nagao Tomokazu,
ItoIhara Toshiko,
IshidaOkawara Akiko,
Uno Kazuko,
Muso Eri,
NagiMiura Noriko,
Ohno Naohito,
Tokunaka Kazuhiro,
Naoe Shiro,
Hashimoto Hiroshi,
Yasuhara Masato,
Yamamoto Kenji,
Suzuki Kazuo
Publication year - 2007
Publication title -
microbiology and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.664
H-Index - 70
eISSN - 1348-0421
pISSN - 0385-5600
DOI - 10.1111/j.1348-0421.2007.tb03933.x
Subject(s) - myeloperoxidase , systemic vasculitis , vasculitis , glomerulonephritis , proteinase 3 , immunology , autoantibody , proinflammatory cytokine , medicine , kidney , rapidly progressive glomerulonephritis , inflammation , pathology , antibody , disease
In systemic vasculitis, the serum level of myeloperoxidase (MPO)‐specific anti‐neutrophil cytoplasmic autoantibodies (MPO‐ANCA) is significantly elevated with the progression of disease. We have established a model of murine systemic vasculitis by administration of MPO‐ANCA and fungal mannoprotein to C57BL/6 mice. We examined the role of MPO and MPO‐ANCA in the pathogenesis of glomerulonephritis and systemic vasculitis in this model using quantum dots (QDs). We demonstrated that QD‐conjugated MPO‐ANCA (ANCA‐QD) visualized the translocation of MPO on the neutrophil membrane surface after stimulation with proinflammatory cytokines. We also observed that MPO translocation on neutrophils in both patients with rapid progressive glomerulonephritis and these model mice without any stimulation, suggesting that MPO translocation is certain to contribute to the development of glomerular lesion. In addition, blood flow on the kidney surface vessel was significantly decelerated in both SCG/Kj mice and this model, suggesting that ANCA induces the damage of blood vessel. These results indicate that MPO‐ANCA and surface‐translocated MPO on the activated neutrophils coordinately plays essential roles in the initial steps of the glomerulonephritis.