Comprehensive investigation of disease‐specific short peptides in sera from patients with systemic sclerosis: Complement C3f‐des‐arginine, detected predominantly in systemic sclerosis sera, enhances proliferation of vascular endothelial cells

Xiang, Ye; Matsui, Toshihiro; Matsuo, Kazuya; Shimada, Kota; Tohma, Shigeto; Nakamura, Hiroshi; Masuko, Kayo; Yudoh, Kazuo; Nishioka, Kusuki; Kato, Tomohiro

doi:10.1002/art.22645

Cited by 37 publications

(24 citation statements)

References 32 publications

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“…Concerns relative to contamination with endotoxin, anaphylatoxins, and various lymphokines and cytokines have been raised. This C3f fragment has recently received more attention as a marker of complement activation in proteomic analyses of peripheral blood proteins in several human diseases (38). In summary, we plan to focus ongoing investigations on three possibilities: namely, properdin interactions with C3b, C3(H 2 O), or iC3b; properdin release via engagement of CR3 or CR4 by iC3b; and properdin mobilization by C3f.…”

Section: Discussionmentioning

confidence: 99%

RETRACTED: Properdin homeostasis requires turnover of the alternative complement pathway

Atkinson

2010

Proc. Natl. Acad. Sci. U.S.A.

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Properdin is a plasma protein and is also released from neutrophil granules following stimulation. At inflammatory sites it can bind bacteria and apoptotic bodies to trigger alternative pathway (AP) activation. Principles governing properdin homeostasis are unknown. We monitored properdin during AP activation and in complement-deficient mice. There was a >90% reduction of properdin in the Crry single-knockout mice ( Crry SKO ). These membrane complement regulatory protein-deficient mice feature accelerated AP turnover, leading to reduced C3 and fB. Injecting cobra venom factor into wild-type mice activated the AP and led to the consumption of C3, fB, and properdin. However, and unexpectedly, properdin was also deficient in C3 −/− , fB −/− , and fD −/− mice. It was present in C1q −/− , C4 −/− , and C5 −/− mice. These findings implicate AP turnover in the maintenance of basal levels of properdin in the blood. To explore the mechanism, classical pathway-activating immune complexes were infused. Within 10 min, properdin was partially restored in fB −/− but not in C3 −/− mice. Markedly reduced properdin in mice deficient in an AP component and its partial restoration by activating C3 suggest a requirement for continuous C3 activation via AP tickover to maintain properdin homeostasis. The mechanism underlying this C3-dependent process was not identified. Engagement of C3a and C5a receptors was ruled out. These findings represent an instructive example of how a positive regulator of an innate immune recognition and effector pathway is controlled. A rationale for such a means to supply properdin for immune reactions is proposed.

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Section: Discussionmentioning

confidence: 99%

RETRACTED: Properdin homeostasis requires turnover of the alternative complement pathway

Atkinson

2010

Proc. Natl. Acad. Sci. U.S.A.

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“…Further studies will aim to determine whether there is a direct correlation between these SLRPs and C3f peptides. C3f peptides had been detected in another recent proteomics study53 using purification of short peptides with C18-bound magnetic beads, in sera of patients with systemic sclerosis (SSc). The authors described a predominance of the C3f-des-Arg form in sera of SSc patients.…”

Section: Discussionmentioning

confidence: 99%

Discovery and biochemical characterisation of four novel biomarkers for osteoarthritis

Seny

Sharif

Fillet

et al. 2011

Annals of the Rheumatic Diseases

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Objective Knee osteoarthritis (OA) is a heterogeneous, complex joint pathology of unknown aetiology. Biomarkers have been widely used to investigate OA but currently available biomarkers lack specifi city and sensitivity. Therefore, novel biomarkers are needed to better understand the pathophysiological processes of OA initiation and progression. Methods Surface enhanced laser desorption/ionisationtime of fl ight-mass spectrometry proteomic technique was used to analyse protein expression levels in 284 serum samples from patients with knee OA classifi ed according to Kellgren and Lawrence (K&L) score (0-4). OA serum samples were also compared to serum samples provided by healthy individuals (negative control subjects; NC; n=36) and rheumatoid arthritis (RA) patients (n=25). Proteins that gave similar signal in all K&L groups of OA patients were ignored, whereas proteins with increased or decreased levels of expression were selected for further studies. Results Two proteins were found to be expressed at higher levels in sera of OA patients at all four K&L scores compared to NC and RA, and were identifi ed as V65 vitronectin fragment and C3f peptide. Of the two remaining proteins, one showed increased expression (unknown protein at m/z of 3762) and the other (identifi ed as connective tissue-activating peptide III protein) was decreased in K&L scores >2 subsets compared to NC, RA and K&L scores 0 or 1 subsets. Conclusion The authors detected four unexpected biomarkers (V65 vitronectin fragment, C3f peptide, CTAP-III and m/z 3762 protein) that could be relevant in the pathophysiological process of OA as having signifi cant correlation with parameters refl ecting local infl ammation and bone remodelling, as well as decrease in cartilage turnover.

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“…Culture media and supplements for HPAEC and HMVEC were obtained from Kurabo Industries (Osaka, Japan). All endothelial cells were cultured in the mixture of their respective media and supplements as described previously [34]. HeLa cells were cultured in Dulbecco's modified Eagle's medium (Sigma‐Aldrich, St Louis, MO, USA) supplemented with 10% fetal bovine serum (HyClone, Logan, UT, USA).…”

Section: Methodsmentioning

confidence: 99%

Peroxiredoxin 2 is a novel autoantigen for anti-endothelial cell antibodies in systemic vasculitis

Karasawa

Kurokawa

Yudoh

et al. 2010

Clinical and Experimental Immunology

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SummaryAnti-endothelial cell antibodies (AECA) have been frequently detected in systemic vasculitis, which affects blood vessels of various sizes. To understand the pathogenic roles of AECA in systemic vasculitis, we attempted to identify target antigens for AECA comprehensively by a proteomic approach. Proteins extracted from human umbilical vein endothelial cells (HUVEC) were separated by two-dimensional electrophoresis, and Western blotting was subsequently conducted using sera from patients with systemic vasculitis. As a result, 53 autoantigenic protein spots for AECA were detected, nine of which were identified by mass spectrometry. One of the identified proteins was peroxiredoxin 2 (Prx2), an anti-oxidant enzyme. Frequency of anti-Prx2 autoantibodies, measured by enzyme-linked immunosorbent assay (ELISA), was significantly higher in systemic vasculitis (60%) compared to those in collagen diseases without clinical vasculitis (7%, P < 0·01) and healthy individuals (0%, P < 0·01). Further, the titres changed in parallel with the disease activity during time-courses. The presence of anti-Prx2 autoantibodies correlated significantly with elevation of serum d-dimers and thrombinantithrombin complex (P < 0·05). Immunocytochemical analysis revealed that live endothelial cells expressed Prx2 on their surface. Interestingly, stimulation of HUVEC with rabbit anti-Prx2 antibodies increased secretion of interleukin (IL)-6, IL-1b, IL-1ra, growth regulated oncogene (GRO)-a, granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colonystimulating factor (GM-CSF), IL-8 and monocyte chemoattractant protein (MCP)-1 more than twofold compared to that of with rabbit immunoglobulin (Ig)G. Taken together, our data suggest that anti-Prx2 autoantibodies would be a useful marker for systemic vasculitis and would be involved in the inflammatory processes of systemic vasculitis.

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Comprehensive investigation of disease‐specific short peptides in sera from patients with systemic sclerosis: Complement C3f‐des‐arginine, detected predominantly in systemic sclerosis sera, enhances proliferation of vascular endothelial cells

Cited by 37 publications

References 32 publications

RETRACTED: Properdin homeostasis requires turnover of the alternative complement pathway

RETRACTED: Properdin homeostasis requires turnover of the alternative complement pathway

Discovery and biochemical characterisation of four novel biomarkers for osteoarthritis

Peroxiredoxin 2 is a novel autoantigen for anti-endothelial cell antibodies in systemic vasculitis

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