Autophagy Mediates the Delivery of Thrombogenic Tissue Factor to Neutrophil Extracellular Traps in Human Sepsis

Kambas, Konstantinos; Mitroulis, Ioannis; Apostolidou, Eirini; Girod, Andreas; Chrysanthopoulou, Akrivi; Pneumatikos, Ioannis; Skendros, Panagiotis; Kourtzelis, Ioannis; Koffa, Maria; Kotsianidis, Ioannis; Ritis, Konstantinos

doi:10.1371/journal.pone.0045427

Reference : Autophagy Mediates the Delivery of Thrombogenic Tissue Factor to Neutrophil Extracell...


	Document type :	Scientific journals : Article
	Discipline(s) :	Life sciences : Biochemistry, biophysics & molecular biology
	To cite this reference:	http://hdl.handle.net/10993/27428

Title :	Autophagy Mediates the Delivery of Thrombogenic Tissue Factor to Neutrophil Extracellular Traps in Human Sepsis
Language :	English
Author, co-author :	Kambas, Konstantinos [First Department of Internal Medicine, Democritus University of Thrace, University General Hospital of Alexandroupolis, Alexandroupolis, Greece]
	Mitroulis, Ioannis [First Department of Internal Medicine, Democritus University of Thrace, University General Hospital of Alexandroupolis, Alexandroupolis, Greece]
	Apostolidou, Eirini [First Department of Internal Medicine, Democritus University of Thrace, University General Hospital of Alexandroupolis, Alexandroupolis, Greece]
	Girod, Andreas [Life Sciences Research Unit-FSTC, University of Luxembourg, Walferdange, Luxembourg]
	Chrysanthopoulou, Akrivi [First Department of Internal Medicine, Democritus University of Thrace, University General Hospital of Alexandroupolis, Alexandroupolis, Greece]
	Pneumatikos, Ioannis [Intensive Care Unit, Democritus University of Thrace, University General Hospital of Alexandroupolis, Alexandroupolis, Greece]
	Skendros, Panagiotis [First Department of Internal Medicine, Democritus University of Thrace, University General Hospital of Alexandroupolis, Alexandroupolis, Greece]
	Kourtzelis, Ioannis [School of Biology, Aristotle University of Thessaloniki, Thessaloniki, Greece]
	Koffa, Maria [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit]
	Kotsianidis, Ioannis [Department of Hematology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece]
	Ritis, Konstantinos [First Department of Internal Medicine, Democritus University of Thrace, University General Hospital of Alexandroupolis, Alexandroupolis, Greece]
Publication date :	2012
Journal title :	PLoS ONE
Volume :	7
Issue/season :	9
Peer reviewed :	Yes (verified by ORBi^lu)
Audience :	International
ISSN :	19326203
Keywords :	[en] RNA ; DNA synthesis ; Escherichia coli ; Gram negative sepsis ; Klebsiella pneumoniae ; Pseudomonas aeruginosa ; RNA isolation ; Autophagy ; Cells, Cultured ; Humans ; Macrolides ; Neutrophils ; Phosphatidylinositol 3-Kinase ; Protein Transport ; Sepsis ; Thromboplastin ; Negibacteria
Abstract :	[en] Background: Sepsis is associated with systemic inflammatory responses and induction of coagulation system. Neutrophil extracellular traps (NETs) constitute an antimicrobial mechanism, recently implicated in thrombosis via platelet entrapment and aggregation. Methodology/Principal Findings: In this study, we demonstrate for the first time the localization of thrombogenic tissue factor (TF) in NETs released by neutrophils derived from patients with gram-negative sepsis and normal neutrophils treated with either serum from septic patients or inflammatory mediators involved in the pathogenesis of sepsis. Localization of TF in acidified autophagosomes was observed during this process, as indicated by positive LC3B and LysoTracker staining. Moreover, phosphatidylinositol 3-kinase inhibition with 3-MA or inhibition of endosomal acidification with bafilomycin A1 hindered the release of TF-bearing NETs. TF present in NETs induced thrombin generation in culture supernatants, which further resulted in protease activated receptor-1 signaling. Conclusions/Significance: This study demonstrates the involvement of autophagic machinery in the extracellular delivery of TF in NETs and the subsequent activation of coagulation cascade, providing evidence for the implication of this process in coagulopathy and inflammatory response in sepsis. © 2012 Kambas et al.
Permalink :	http://hdl.handle.net/10993/27428
DOI :	10.1371/journal.pone.0045427

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