Endotoxaemia-augmented murine venous thrombosis is dependent on TLR-4 and ICAM-1, and potentiated by neutropenia

• DOI: 10.1160/th16-03-0218
• Publication Date: 2016-12-15T10:42:54Z
• Authors: Andrea T. Obi; Elizabeth Andraska; Yogendra Kanthi; Chase W. Kessinger; Megan Elfline; Cathy Luke; Teruna J. Siahaan; Farouc A. Jaffer; Thomas W. Wakefield; Peter K. Henke
• Keywords: Neutrophil Extracellular Traps; Venous stasis

Venous thromboembolism is a major cause of death during and immediately post-sepsis. thrombosis (VT) mediated by cell adhesion molecules leukocytes, including neutrophil extracellular traps (NETs). Sepsis, or experimentally, endotoxaemia, shares similar characteristics modulated via toll like receptor 4 (TLR4). This study was undertaken to determine if endotoxaemia potentiates early stasis thrombogenesis, secondarily the role VT TLR4, ICAM-1 neutrophils (PMNs). Wild-type (WT), ICAM-1-/- TLR4-/- mice underwent treatment with saline LPS (10 mg/kg i. p.) alone, followed inferior vena cava (IVC) ligation generate VT. In vivo microscopy leukocyte trafficking performed in non-thrombosed mice, tissue plasma were harvested formation. Pre-thrombosis, circulating elevated increased rolling occurred on IVC LPS-treated mice. Post-thrombosis, endotoxaemic formed larger, platelet-poor thrombi. Endotoxaemic did not have an augmented thrombotic response exhibited significantly decreased compared WT controls. had smaller thrombi Hypothesising that PMNs localised inflamed endothelium promoting thrombosis, PMN depletion using anti-Ly6G antibody performed. Paradoxically, without amplified, potentially related induced elevation PAI-1 FXIII, uPA. Endotoxaemia enhanced occurs TLR-4 dependent fashion, potentiated neutropenia. and/or inhibition may be unique strategy prevent sepsis-associated