Shiga toxin enhances functional tissue factor on human glomerular endothelial cells: implications for the pathophysiology of hemolytic uremic syndrome

• Published in: Journal of thrombosis and haemostasis 2005-04, Vol.3 (4), p.752-762
• Main Authors: NESTORIDI, E., TSUKUROV, O., KUSHAK, R. I., INGELFINGER, J. R., GRABOWSKI, E. F.
• Format: Article
• Language: English
• Subjects: Cell Membrane - metabolism; Cells, Cultured; Chromogenic Compounds - chemistry; endothelial cells; Endothelium, Vascular - cytology; Endothelium, Vascular - metabolism; Epithelial Cells - metabolism; Factor Xa - chemistry; Fibronectins - metabolism; hemolytic uremic syndrome; Hemolytic-Uremic Syndrome - physiopathology; Humans; Kidney Glomerulus - cytology; Kidney Glomerulus - metabolism; Lipoproteins - metabolism; Microcirculation; Microscopy, Fluorescence; Reverse Transcriptase Polymerase Chain Reaction; RNA - metabolism; RNA, Messenger - metabolism; Shiga toxin; Shiga Toxin 1 - metabolism; Shiga Toxin 1 - pharmacology; Thromboplastin - biosynthesis; Thromboplastin - metabolism; Time Factors; tissue factor; Tumor Necrosis Factor-alpha - metabolism; Umbilical Veins - cytology; Up-Regulation
• ISSN: 1538-7933; 1538-7836; 1538-7836
• DOI: 10.1111/j.1538-7836.2005.01205.x

Background: The pathogenesis of Shiga toxin (Stx)‐mediated childhood hemolytic uremic syndrome (HUS) is not fully delineated, although current evidence implicates a prothrombotic state. We hypothesized that the tissue factor (TF) pathway plays a major role in the pathophysiology of HUS. Materials and methods: We measured cell surface TF activity in response to tumor necrosis factor‐α (TNF‐α) (20 ng mL−1, 2–144 h), Stx‐1 (10−11 mol L−1, 4–144 h), or their combination (TNF‐α 22 h and Stx‐1 for the last 0.5–4 h of TNF‐α incubation) on human glomerular (microvascular) endothelial cells (HGECs) and human umbilical vein (macrovascular) endothelial cells (HUVECs). Results and conclusions: We observed that while TNF‐α caused an increase in cell surface TF activity on both cell types, the combination of TNF‐α and Stx‐1 differentially affected HGECs. On these cells, TF activity was increased further by 2.67 ± 0.38‐fold (n = 38, P