Interaction of Shiga Toxin with the A-domains and Multimers of von Willebrand Factor |
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| Authors: | Nathan C. Lo Nancy A. Turner Miguel A. Cruz Joel Moake |
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| Affiliation: | From the ‡Department of Bioengineering, Rice University, Houston, Texas 77005.;the §Section of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, and ;the ¶Center for Translational Research in Inflammatory Diseases, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas 77030 |
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| Abstract: | Shiga toxin (Stx) produced by enterohemorrhagic Escherichia coli causes diarrhea-associated hemolytic-uremic syndrome (DHUS), a severe renal thrombotic microangiopathy. We investigated the interaction between Stx and von Willebrand Factor (VWF), a multimeric plasma glycoprotein that mediates platelet adhesion, activation, and aggregation. Stx bound to ultra-large VWF (ULVWF) secreted from and anchored to stimulated human umbilical vein endothelial cells, as well as to immobilized VWF-rich human umbilical vein endothelial cell supernatant. This Stx binding was localized to the A1 and A2 domain of VWF monomeric subunits and reduced the rate of ADAMTS-13-mediated cleavage of the Tyr1605-Met1606 peptide bond in the A2 domain. Stx-VWF interaction and the associated delay in ADAMTS-13-mediated cleavage of VWF may contribute to the pathophysiology of DHUS. |
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| Keywords: | Adamts13 Platelets Thrombosis Toxins Von Willebrand Factor Hemolytic Uremia Shiga Toxin |
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