Up-regulation of adhesion molecule expression in glomerular endothelial cells by anti-myeloperoxidase antibody

Nagao, Tomokazu; Matsumura, Mimiko; Mabuchi, Ayako; Ishida-Okawara, Akiko; Koshio, Osamu; Nakayama, Toshinori; Minamitani, Haruyuki; Suzuki, Kazuo

doi:10.1093/ndt/gfl555

Cited by 38 publications

(29 citation statements)

References 38 publications

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“…Especially in kidney, immunohistochemical staining showed that neutrophils located around the fringe of glomeruli with the development of mesangiolysis. To support this, we have previously reported that MPO-ANCA directly bound to primary glomerular endothelium following upregulation of ICAM-1, VCAM-1, E-selectin, and promotion of TNF-α production (35). These results are consistent with the observation of Little et al (31) that MPO-ANCA on leukocytes interacts with vascular endothelium via ICAM-1 in systemic vasculitis rats with developed MPO-ANCA.…”

Section: Discussionsupporting

confidence: 86%

“…This is consistent with our previous results that MPO-ANCA was directly bound with glomerular endothelium and upregulated some adhesion molecules, including ICAM-1, VCAM-1, and Eselectin (35). In contrast, ANCA-QD was highly accumulated to the CD11b ϩ macrophage cluster in lung inflammatory lesion (Fig.…”

Section: Qd-conjugated Mpo-anca Are Detected On Activated Neutrophilssupporting

confidence: 93%

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Trafficking of QD‐Conjugated MPO‐ANCA in Murine Systemic Vasculitis and Glomerulonephritis Model Mice

Hoshino

Nagao

Ito‐Ihara

et al. 2007

Microbiology and Immunology

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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.

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Section: Discussionsupporting

confidence: 86%

Section: Qd-conjugated Mpo-anca Are Detected On Activated Neutrophilssupporting

confidence: 93%

Trafficking of QD‐Conjugated MPO‐ANCA in Murine Systemic Vasculitis and Glomerulonephritis Model Mice

Hoshino

Nagao

Ito‐Ihara

et al. 2007

Microbiology and Immunology

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“…[125][126][127][128] In vitro studies show that cytokines, released in response to infections, prime neutrophils and upregulate adhesion molecules on neutrophils and endothelial cells (L and E selectins, respectively) to facilitate localization in glomerular capillaries. 129,130 Cytokine-primed neutrophils redistribute cytoplasmic primary granules containing MPO and PR3 to the cell surface where ANCA IgG binds directly or through Fc, Fab'2, or neutrophil-specific Mac-1 receptors activating a respiratory burst with release of cationic MPO and PR3 as well as other proteases and oxidants. [129][130][131][132][133][134][135] Neutrophil extracellular traps (NETs) are also formed containing entrapped MPO, PR3, and MPO DNA in a chromatin web and these can mediate injury directly through TLRs as well as modulate the immune response.…”

Section: T Cellsmentioning

confidence: 99%

“…129,130 Cytokine-primed neutrophils redistribute cytoplasmic primary granules containing MPO and PR3 to the cell surface where ANCA IgG binds directly or through Fc, Fab'2, or neutrophil-specific Mac-1 receptors activating a respiratory burst with release of cationic MPO and PR3 as well as other proteases and oxidants. [129][130][131][132][133][134][135] Neutrophil extracellular traps (NETs) are also formed containing entrapped MPO, PR3, and MPO DNA in a chromatin web and these can mediate injury directly through TLRs as well as modulate the immune response. 134,136 In ANCA-GN, NETs are present in the circulation and in glomeruli co-localized with neutrophils and DCs, and anti-NET antibodies are present along with circulating MPO-DNA complexes (nucleosomes).…”

Section: T Cellsmentioning

confidence: 99%

Basic and Translational Concepts of Immune-Mediated Glomerular Diseases

Couser

2012

Journal of the American Society of Nephrology

179

155

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Genetically modified immune responses to infections and self-antigens initiate most forms of GN by generating pathogen-and danger-associated molecular patterns that stimulate Toll-like receptors and complement. These innate immune responses activate circulating monocytes and resident glomerular cells to release inflammatory mediators and initiate adaptive, antigen-specific immune responses that collectively damage glomerular structures. CD4 T cells are needed for B cell-driven antibody production that leads to immune complex formation in glomeruli, complement activation, and injury induced by both circulating inflammatory and resident glomerular effector cells. Th17 cells can also induce glomerular injury directly. In this review, information derived from studies in vitro, well characterized experimental models, and humans summarize and update likely pathogenic mechanisms involved in human diseases presenting as nephritis (postinfectious GN, IgA nephropathy, antiglomerular basement membrane and antineutrophil cytoplasmic antibodymediated crescentic GN, lupus nephritis, type I membranoproliferative GN), and nephrotic syndrome (minimal change/FSGS, membranous nephropathy, and C3 glomerulopathies). Advances in understanding the immunopathogenesis of each of these entities offer many opportunities for future therapeutic interventions.

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“…Because ANCA-associated glomerulonephritis could be diagnosed only with a positive ANCA titer and signs of nephritis (such as active urinary sediment and elevated serum creatinine), if we knew in advance that nearly 100% of patients would receive aggressive therapy after the histologic diagnosis by KBx, we could consider KBx not necessary for a diagnosis of ANCA-associated glomerulonephritis. In fact, since Nagao et al reported that anti-MPO antibody directly activated glomerular endothelial cells 14) , it was highly possible that the patients with abnormal urinary findings had ANCAassociated glomerulonephritis if serum ANCA, particularly MPO-ANCA, was positive. In addition, histopathologic classification of ANCA-associated glomerulonephritis has been shown to predict survival differences, but KBX-based therapeutic strategies have not been explored 15) .…”

Section: Discussionmentioning

confidence: 99%

Safety and Utility of Kidney Biopsy in Elderly Patients: A Single-Center Cohort Study

Suzuki

Tsuruoka

Ichikawa

et al. 2015

J St. Marianna Univ

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BACKGROUND The number of elderly patients with kidney disease is increasing rapidly, and we often encounter situations in which we need to weigh the benefits and risks of kidney biopsy (KBx). The decision is often difficult because reports addressing the safety and utility of KBx in the elderly are scarce. METHODS This observational study included 548 consecutive adult patients who underwent native KBx. We divided the patients into an E group, elderly patients 65 years or older, and an NE group, the remaining nonelderly patients. Baseline characteristics and complications of KBx were compared between the two groups. We also investigated the proportions of patients in whom steroid and/or immunosuppressive treatment was started after KBx. RESULTS There were 112 patients in the E group and 436 in the NE group. The baseline values differed significantly between the groups for age (71.5 ± 4.7 vs. 39.6 ± 13.9 years), estimated glomerular filtration rate (eGFR) (41.4 ± 27.1 vs. 72.0 ± 33.7 ml/min/1.73 m 2 ), proportion of patients with diabetes (25.0% vs. 4.8%), and proportion of those who underwent surgical KBx (11.6% vs 3.0%), There was no significant difference in terms of sex.The E group experienced slightly more major complications (4.0% vs. 1.2%, p=0.05) but fewer minor complications (2.0% vs. 6.0%, p=0.10) with percutaneous KBx than the NE group did, although neither major nor minor complications occurred in patients who underwent surgical KBx. Final diagnoses after KBx, such as IgA nephropathy, IgA vasculitis, and ANCA-associated glomerulonephritis, were associated with various clinical diagnoses, indicating that the final diagnoses could not have been obtained without KBx. Treatment with steroid and/or immunosuppressant was required to a high degree in patients with ANCA-associated glomerulonephritis and minimal change disease after histologic evaluation by KBx. CONCLUSIONS The risk of KBx in the elderly patients was significantly higher than that in the non-elderly, and some diagnoses could not have been obtained without KBx. Thus, as long as nephrologists perform KBx cautiously according to strict indications, KBx can be a safe and useful option in the management of kidney disease in the elderly.

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Up-regulation of adhesion molecule expression in glomerular endothelial cells by anti-myeloperoxidase antibody

Cited by 38 publications

References 38 publications

Trafficking of QD‐Conjugated MPO‐ANCA in Murine Systemic Vasculitis and Glomerulonephritis Model Mice

Trafficking of QD‐Conjugated MPO‐ANCA in Murine Systemic Vasculitis and Glomerulonephritis Model Mice

Basic and Translational Concepts of Immune-Mediated Glomerular Diseases

Safety and Utility of Kidney Biopsy in Elderly Patients: A Single-Center Cohort Study

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