Proteomic analysis of neutrophils in ANCA-associated vasculitis reveals a dysregulation in proteinase 3-associated proteins such as annexin-A1 involved in apoptotic cell clearance

被引:33
作者
Everts-Graber, Judith [1 ,2 ,3 ,4 ]
Martin, Katherine R. [1 ,2 ,3 ]
Thieblemont, Nathalie [1 ,2 ,3 ]
Mocek, Julie [1 ,2 ,3 ]
Roccabianca, Arnaud [1 ,2 ,3 ]
Chafey, Philippe [1 ,2 ,3 ]
Le Gall, Morgane [1 ,2 ,3 ]
Tacnet-Delorme, Pascale [5 ]
Reutelingsperger, Chris P. [6 ]
Naccache, Jean-Marc [7 ]
Bonnotte, Bernard [8 ]
Karras, Alexandre [3 ,9 ]
Puechal, Xavier [1 ,2 ,3 ,10 ,11 ]
Guillevin, Loic [10 ,11 ]
Terrier, Benjamin [1 ,2 ,3 ,10 ,11 ]
Frachet, Philippe [5 ]
Perretti, Mauro [12 ]
Mouthon, Luc [1 ,2 ,3 ,10 ,11 ]
Witko-Sarsat, Veronique [1 ,2 ,3 ]
机构
[1] INSERM, Inst Cochin, U1016, Paris, France
[2] CNRS, UMR 8104, Paris, France
[3] Univ Paris 05, Sorbonne Paris Cite, Paris, France
[4] Univ Hosp Bern, Dept Rheumatol & Immunol, Bern, Switzerland
[5] Univ Grenoble Alpes, CNRS, IBS, CEA, Grenoble, France
[6] Maastricht Univ, Cardiovasc Res Inst Maastricht, Dept Biochem, Maastricht, Netherlands
[7] Hop Tenon, AP HP, Dept Pneumol, Paris, France
[8] CHU Dijon, Serv Med Interne & Immunol Clin, Dijon, France
[9] Hop Europeen Georges Pompidou, AP HP, Dept Nephrol, Paris, France
[10] AP HP, Pole Med Interne, Fac Med, Paris, France
[11] AP HP, Ctr Reference Vasc Necrosantes & Sclerode, Paris, France
[12] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, Charterhouse Sq, London EC1M 6BQ, England
基金
澳大利亚国家健康与医学研究理事会;
关键词
annexin A; calreticulin; neutrophil; phospholipid scramblase 1; proteinase; 3; vasculitis; MEMBRANE PROTEINASE-3; AUTOANTIGEN GENES; EXPRESSION; GRANULOMATOSIS; CALPROTECTIN; PHAGOCYTOSIS; POLYANGIITIS; RELAPSE; LIGAND;
D O I
10.1016/j.kint.2019.02.017
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Granulomatosis with polyangiitis (GPA) is an autoimmune vasculitis associated with anti-neutrophil-cytoplasmic antibodies (ANCA) against proteinase 3 leading to kidney damage. Neutrophils from those patients have increased expression of membrane proteinase 3 during apoptosis. Here we examined whether neutrophils from patients with GPA have dysregulated protein expressions associated with apoptosis. A global proteomic analysis was performed comparing neutrophils from patients with GPA, with healthy individuals under basal conditions and during apoptosis. At disease onset, the cytosolic proteome of neutrophils of patients with GPA before treatment was significantly different from healthy controls, and this dysregulation was more pronounced following ex vivo apoptosis. Proteins involved in cell death/survival were altered in neutrophils of patients with GPA. Several proteins identified were PR3-binding partners involved in the clearance of apoptotic cells, namely calreticulin, annexin-A1 and phospholipid scramblase 1. These proteins form a platform at the membrane of apoptotic neutrophils in patients with GPA but not healthy individuals and this was associated with the clinical presentation of GPA. Thus, our study shows that neutrophils from patients with GPA have an intrinsic dysregulation in proteins involved in apoptotic cell clearance, which could contribute to the unabated inflammation and autoimmunity in GPA. Hence, harnessing these dysregulated pathways could lead to novel biomarkers and targeted therapeutic opportunities to treat kidney disease.
引用
收藏
页码:397 / 408
页数:12
相关论文
共 52 条
[1]   Elevated neutrophil membrane expression of proteinase 3 is dependent upon CD177 expression [J].
Abdgawad, M. ;
Gunnarsson, L. ;
Bengtsson, A. A. ;
Geborek, P. ;
Nilsson, L. ;
Segelmark, M. ;
Hellmark, T. .
CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2010, 161 (01) :89-97
[2]   Decreased Neutrophil Apoptosis in Quiescent ANCA-Associated Systemic Vasculitis [J].
Abdgawad, Mohamed ;
Pettersson, Asa ;
Gunnarsson, Lena ;
Bengtsson, Anders A. ;
Geborek, Pierre ;
Nilsson, Lars ;
Segelmark, Marten ;
Hellmark, Thomas .
PLOS ONE, 2012, 7 (03)
[3]   Calprotectin as a Biomarker for Rheumatoid Arthritis: A Systematic Review [J].
Abildtrup, Mads ;
Kingsley, Gabrielle H. ;
Scott, David L. .
JOURNAL OF RHEUMATOLOGY, 2015, 42 (05) :760-770
[4]   Apoptotic neutrophils and T cells sequester chemokines during immune response resolution through modulation of CCR5 expression [J].
Ariel, Amiram ;
Fredman, Gabrielle ;
Sun, Yee-Ping ;
Kantarci, Alpdogan ;
Van Dyke, Thomas E. ;
D Luster, Andrew ;
Serhan, Charles N. .
NATURE IMMUNOLOGY, 2006, 7 (11) :1209-1216
[5]   Annexin I is an endogenous ligand that mediates apoptotic cell engulfment [J].
Arur, S ;
Uche, UE ;
Rezaul, K ;
Fong, M ;
Scranton, V ;
Cowan, AE ;
Mohler, W ;
Han, DK .
DEVELOPMENTAL CELL, 2003, 4 (04) :587-598
[6]   Constitutive Neutrophil Apoptosis: Regulation by Cell Concentration via S100 A8/9 and the MEK - ERK Pathway [J].
Atallah, Mizhir ;
Krispin, Alon ;
Trahtemberg, Uriel ;
Ben-Hamron, Sandrine ;
Grau, Amir ;
Verbovetski, Inna ;
Mevorach, Dror .
PLOS ONE, 2012, 7 (02)
[7]  
BLOCH DA, 1990, ARTHRITIS RHEUM, V33, P1068
[8]   Epigenetic basis for aberrant upregulation of autoantigen genes in humans with ANCA vasculitis [J].
Ciavatta, Dominic J. ;
Yang, JiaJin ;
Preston, Gloria A. ;
Badhwar, Anshul K. ;
Xiao, Hong ;
Hewins, Peter ;
Nester, Carla M. ;
Pendergraft, William F., III ;
Magnuson, Terry R. ;
Jennette, J. Charles ;
Falk, Ronald J. .
JOURNAL OF CLINICAL INVESTIGATION, 2010, 120 (09) :3209-3219
[9]   Ligand-specific conformational change of the G-protein-coupled receptor ALX/FPR2 determines proresolving functional responses [J].
Cooray, Sadani N. ;
Gobbetti, Thomas ;
Montero-Melendez, Trinidad ;
McArthur, Simon ;
Thompson, Dawn ;
Clark, Adrian J. L. ;
Flower, Roderick J. ;
Perretti, Mauro .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2013, 110 (45) :18232-18237
[10]  
DRANSFIELD I, 1994, J IMMUNOL, V153, P1254