Direct activation of glomerular endothelial cells by anti-moesin activity of anti-myeloperoxidase antibody

Nagao, Tomokazu; Suzuki, Koya; Utsunomiya, Kentaro; Matsumura, Mimiko; Saiga, Kan; Wang, Pichao; Minamitani, Haruyuki; Aratani, Yasuaki; Nakayama, Toshinori; Suzuki, Kazuo

doi:10.1093/ndt/gfr032

Cited by 47 publications

(42 citation statements)

References 37 publications

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“…Given the cross-reaction to moesin of anti-MPO antibody [8], we studied whether the binding of anti-MPO mAb to GEnCs increased with the treatment of HMGB1.…”

Section: Resultsmentioning

confidence: 99%

“…Nagao et al identified a cross-reactive molecule on mouse GEnCs, which could be recognized by anti-MPO antibody, termed moesin [8]. They assumed that moesin shares certain similar sequences with those on the N-terminal region of the MPO heavy chain.…”

Section: Discussionmentioning

confidence: 99%

“…ANCAs are proved to be involved in inducing and amplifying neutrophil-mediated endothelial injury in AAV [4, 5]. Nevertheless, there is also evidence supporting the direct ability of MPO-ANCA to produce vessel damage [6–8]. …”

Section: Introductionmentioning

confidence: 99%

“…Moesin, with the full name of membrane-organizing extension spike protein, is previously described as a cytoskeletal protein that belongs to the ezrin–radixin–moesin (ERM) family, which could function as links between the plasma membrane and the actin cytoskeleton [19]. More interestingly, Nagao et al recently reported a direct activation of mouse GEnCs by anti-moesin activity of anti-MPO antibody [8]. In their study, the authors identified a cross-reactive molecule, which could be recognized by anti-MPO antibody, existing on mouse GEnCs.…”

Section: Introductionmentioning

confidence: 99%

“…In their study, the authors identified a cross-reactive molecule, which could be recognized by anti-MPO antibody, existing on mouse GEnCs. Later, the molecule was confirmed as moesin by mass spectrometry [8]. Given the potential effect of HMGB1 on upgrading moesin and the anti-moesin activity of anti-MPO antibody on GEnCs, we hypothesized that there is a moesin-dependent way through which HMGB1 can contribute to MPO-ANCA-induced GEnC injury.…”

Section: Introductionmentioning

confidence: 99%

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High mobility group box-1 contributes to anti-myeloperoxidase antibody-induced glomerular endothelial cell injury through a moesin-dependent route

Deng

Wang²,

Chang³

et al. 2017

Arthritis Res Ther

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BackgroundOur previous study found that circulating and urinary levels of high mobility group box-1 (HMGB1) were closely associated with disease activity in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Moreover, HMGB1 participates in ANCA-induced neutrophil activation. Cross-reactivity between moesin and anti-myeloperoxidase (MPO) antibody has been reported in both human and mouse. The current study investigated whether HMGB1 participated in MPO-ANCA-induced glomerular endothelial cell (GEnC) injury, which is one of the most important aspects in the pathogenesis of AAV.MethodsThe effects of HMGB1 on expression of moesin on GEnCs and anti-MPO antibody binding to GEnCs were measured. MPO expression on GEnCs was explored. The effects of HMGB1 in MPO-ANCA induced GEnC injury were measured, during which the role of moesin was explored. Antagonists for various relevant receptors were employed.ResultsSera from AAV patients at the active stage could mediate GEnC injury, while this effect could be attenuated by preblocking HMGB1. HMGB1 could increase the expression of moesin on GEnCs and the binding of anti-MPO antibody to moesin. The colocalization of moesin expression and anti-MPO antibody binding can be detected. Little, if any, MPO was expressed in GEnCs. HMGB1 increased GEnC activation and injury in the presence of patient-derived MPO-ANCA-positive IgGs through moesin. The effects of HMGB1 on expression of moesin on GEnCs, anti-MPO antibody binding to GEnCs, GEnC activation and injury were mainly toll like receptor 4 (TLR4) dependent.ConclusionsHMGB1 can increase the expression of moesin but not MPO on GEnCs, and can further participate in MPO-ANCA-induced GEnC activation and injury by cross-reactivity between moesin and anti-MPO antibody.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-017-1339-4) contains supplementary material, which is available to authorized users.

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“…Given the cross-reaction to moesin of anti-MPO antibody [8], we studied whether the binding of anti-MPO mAb to GEnCs increased with the treatment of HMGB1.…”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

High mobility group box-1 contributes to anti-myeloperoxidase antibody-induced glomerular endothelial cell injury through a moesin-dependent route

Deng

Wang²,

Chang³

et al. 2017

Arthritis Res Ther

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Remarks on the Asia Pacific Meeting of Vasculitis and ANCA Workshop 2012

Suzuki

2013

Clin Exp Nephrol

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An international meeting, The Asia Pacific Meeting of Vasculitis and ANCA Workshop 2012, was held on March 28-31, 2012 at Shinagawa, Tokyo, Japan. The meeting focused on vasculitis and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis in the Asia-Pacific area. This was a high-profile event and attracted scientists and physicians from around the world, all of whom are committed to the care of patients with vasculitis, ANCA and related diseases. The Asia Pacific international meeting was able to extend insights into Kawasaki disease, Takayasu arteritis, and myeloperoxidase ANCA-associated vasculitis. The program addressed the multidisciplinary nature of vasculitis, including genomics, genetics, pathogenesis, epidemiology, biomarkers, clinical features, and therapeutic trials.

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Proposal of anti-moesin as a novel biomarker for ANCA-associated vasculitis

Suzuki

Nagao

et al. 2013

Clin Exp Nephrol

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Myeloperoxidase (MPO)-specific antineutrophil cytoplasmic antibody (ANCA) is associated with rapidly progressive glomerulonephritis (RPGN) in microscopic polyangiitis (MPA). MPO-ANCA activates neutrophils by binding to cell surface MPO expressed on tumor necrosis factor-α (TNF-α)-primed neutrophils and induces neutrophil degranulation and production of reactive oxygen species, consequently resulting in glomerular endothelial damage. Recently, anti-MPO antibody has been found to activate glomerular endothelial cells, leading to an upregulation of adhesion molecules. MPO-ANCA, however, is not always correlated with disease activity in MPA. Accordingly, the molecule(s) responsible for the anti-MPO antibody have been explored on mouse glomerular endothelial cells. The molecule was identified as moesin, which is a heparin-binding protein and belongs to the ezrin/radixin/moesin family of proteins distributed in the plasma membrane in the cellular cortex. Interestingly, anti-moesin is observed in sera of SCG/Kj mice, which spontaneously develop MPO-ANCA-associated RPGN, and of patients with MPO-AAV. The activation of glomerular endothelial cells by the anti-MPO antibody appears to be associated with signaling through moesin.

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Direct activation of glomerular endothelial cells by anti-moesin activity of anti-myeloperoxidase antibody

Abstract: The endothelial CXC chemokines, KC and MIP-2, contribute to infiltration of neutrophils in MPO-ANCA-associated vasculitis involving glomerulonephritis. The activation of glomerular endothelial cells by anti-MPO IgG appeared to directly involve a signaling through moesin.

Cited by 47 publications

References 37 publications

High mobility group box-1 contributes to anti-myeloperoxidase antibody-induced glomerular endothelial cell injury through a moesin-dependent route

High mobility group box-1 contributes to anti-myeloperoxidase antibody-induced glomerular endothelial cell injury through a moesin-dependent route

Remarks on the Asia Pacific Meeting of Vasculitis and ANCA Workshop 2012

Proposal of anti-moesin as a novel biomarker for ANCA-associated vasculitis

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