Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/61298
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Type: Journal article
Title: Tissue factor-dependent procoagulant activity of subtilase cytotoxin, a potent AB5 toxin produced by shiga toxigenic Escherichia coli
Author: Wang, H.
Paton, J.
Thorpe, C.
Bonder, C.
Sun, W.
Paton, A.
Citation: Journal of Infectious Diseases, 2010; 202(9):1415-1423
Publisher: Univ Chicago Press
Issue Date: 2010
ISSN: 0022-1899
1537-6613
Statement of
Responsibility: 
Hui Wang, James C. Paton, Cheleste M. Thorpe, Claudine S. Bonder, Wai Yan Sun, and Adrienne W. Paton
Abstract: Subtilase cytotoxin (SubAB), produced by certain virulent Shiga toxigenic Escherichia coli strains, causes hemolytic uremic syndrome–like pathology in mice, including extensive microvascular thrombosis. SubAB acts by specifically cleaving the essential endoplasmic reticulum chaperone binding immunoglobulin protein (BiP). BiP has been reported to inhibit the activation of tissue factor (TF), the major initiator of extrinsic coagulation. We hypothesized that the apparent prothrombotic effect of SubAB in vivo may involve the stimulation of TF‐dependent procoagulant activity. TF‐dependent procoagulant activity, TF messenger RNA (mRNA) levels, and BiP cleavage were therefore examined in human macrophage cells and primary human umbilical vein endothelial cells exposed to SubAB. In both types of cells, SubAB significantly increased TF‐dependent procoagulant activity, induced TF mRNA expression, and mediated BiP cleavage. No effects were seen when cells were treated with a nonproteolytic mutant toxin, SubAA272B. Our results suggest that the procoagulant effect of SubAB may be dependent on both the up‐regulation of TF expression and the activation of TF by means of BiP cleavage.
Keywords: Cells, Cultured
Macrophages
Endothelial Cells
Animals
Humans
Mice
Thrombosis
Subtilisins
Escherichia coli Proteins
Thromboplastin
Heat-Shock Proteins
Gene Expression Profiling
Blood Coagulation
Shiga-Toxigenic Escherichia coli
Rights: © 2010 by the Infectious Diseases Society of America
DOI: 10.1086/656534
Appears in Collections:Aurora harvest
Molecular and Biomedical Science publications

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