Tissue factor expression in neutrophil extracellular traps and neutrophil derived microparticles in antineutrophil cytoplasmic antibody associated vasculitis may promote thromboinflammation and the thrombophilic state associated with the disease
- Resource Type
- Authors
- Panagiotis Skendros; Konstantinos Kambas; Akrivi Chrysanthopoulou; Lydia Nakopoulou; Andreas Girod; Eirini Apostolidou; Stella Arelaki; Maria Koffa; Konstantinos Ritis; Marios Froudarakis; Dimitrios T. Boumpas; Dimitrios Vassilopoulos; Ioannis Mitroulis; Prodromos Sidiropoulos; Alexandra Giatromanolaki
- Source
- Annals of the rheumatic diseases. 73(10)
- Subject
- Adult
Male
Pathology
medicine.medical_specialty
Neutrophils
Immunology
Inflammation
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Extracellular Traps
General Biochemistry, Genetics and Molecular Biology
Neutrophil Activation
Flow cytometry
Antibodies, Antineutrophil Cytoplasmic
Thromboplastin
Tissue factor
Rheumatology
Cell-Derived Microparticles
medicine
Immunology and Allergy
Humans
Thrombophilia
Anti-neutrophil cytoplasmic antibody
Aged
biology
medicine.diagnostic_test
business.industry
Tumor Necrosis Factor-alpha
Remission Induction
Neutrophil extracellular traps
Middle Aged
medicine.disease
Bronchoalveolar lavage
Case-Control Studies
Immunoglobulin G
biology.protein
Female
Antibody
medicine.symptom
Vasculitis
business
Bronchoalveolar Lavage Fluid
- Language
- ISSN
- 1468-2060
Objectives Antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) is characterised by neutrophil activation. An elevated prevalence of venous thromboembolic events has been reported in AAV. Because of the critical role of neutrophils in inflammation associated thrombosis, we asked whether neutrophil tissue factor (TF) may be implicated in the thrombotic diathesis in AAV. Methods Neutrophils from four patients and sera from 17 patients with ANCA associated vasculitis with active disease and remission were studied. TF expression was assessed by immunoblotting and confocal microscopy. Circulating DNA levels were evaluated. TF expressing microparticles (MPs) were measured by flow cytometry and thrombin–antithrombin complex levels by ELISA. Results Peripheral blood neutrophils from four patients with active disease expressed elevated TF levels and released TF expressing neutrophil extracellular traps (NETs) and MPs. TF positive NETs were released by neutrophils isolated from the bronchoalveolar lavage and were detected in nasal and renal biopsy specimens. Elevated levels of circulating DNA and TF expressing neutrophil derived MPs were further observed in sera from patients with active disease. Induction of remission attenuated the aforementioned effects. Control neutrophils treated with sera from patients with active disease released TF bearing NETs and MPs which were abolished after IgG depletion. Treatment of control neutrophils with isolated IgG from sera from patients with active disease also resulted in the release of TF bearing NETs. TF implication in MP dependent thrombin generation was demonstrated by antibody neutralisation studies. Conclusions Expression of TF in NETs and neutrophil derived MPs proposes a novel mechanism for the induction of thrombosis and inflammation in active AAV.