Neutrophil Extracellular Traps Drive Endothelial-to-Mesenchymal Transition

• DOI: 10.1161/atvbaha.117.309002
• Publication Date: 2017-05-12T01:10:52Z
• Authors: Elmar Pieterse; Nils Rother; Marjolein Garsen; Julia M. Hofstra; Simon C. Satchell; Markus Hoffmann; Markus A. Loeven; Hanneke K. Knaapen; Olivier W.H. van ...; Jo H.M. Berden; Luuk B. Hilbrands; Johan van der Vlag
• Keywords: Neutrophil Extracellular Traps; Endothelial Dysfunction; Neutrophil elastase

An excessive release and impaired degradation of neutrophil extracellular traps (NETs) leads to the continuous exposure NETs endothelium in a variety hematologic autoimmune disorders, including lupus nephritis. This study aims unravel mechanisms through which jeopardize vascular integrity.Microvascular macrovascular endothelial cells were exposed NETs, subsequent effects on integrity function determined vitro vivo. We found that have limited capacity internalize via receptor for advanced glycation endproducts. overflow phagocytic resulted persistent presence rapidly altered cell-cell contacts induced leakage transendothelial albumin passage elastase-mediated proteolysis intercellular junction protein VE-cadherin. Furthermore, NET-associated elastase promoted nuclear translocation junctional β-catenin endothelial-to-mesenchymal transition cultured cells. In vivo, could be identified kidney samples diseased MRL/lpr mice patients with nephritis, whom glomerular correlated severity proteinuria transition.These results indicate an excess exceeds promotes VE-cadherin activation signaling. Our data designate as potential therapeutic target prevention alterations diseases characterized by aberrant NET release.