Shiga toxin B subunits induce VWF secretion by human endothelial cells and thrombotic microangiopathy in ADAMTS13-deficient mice.

Blood
Jing HuangJ Evan Sadler

Abstract

Diarrhea-associated hemolytic uremic syndrome (D+HUS) is the most common cause of acute renal failure among children. Renal damage in D+HUS is caused by Shiga toxin (Stx), which is elaborated by Shigella dysenteriae and certain strains of Escherichia coli, in North America principally E coli O157:H7. Recent studies demonstrate that Stx also induces von Willebrand factor (VWF) secretion by human endothelial cells and causes thrombotic thrombocytopenic purpura, a disease with similarities to D+HUS, in Adamts13(-/-) mice. Stx occurs in 2 variants, Stx1 and Stx2, each of which is composed of 1 catalytically active A subunit that is responsible for cytotoxicity, and 5 identical B subunits that mediate binding to cell-surface globo-triaosylceramide. We now report that B subunits from Stx1 or Stx2 can stimulate the acute secretion of VWF in the absence of the cytotoxic A subunit. This rapid effect requires binding and clustering of globotriaosylceramide, and depends on plasma membrane cholesterol and caveolin-1 but not clathrin. Furthermore, similar to Stx2 holotoxin, the isolated Stx2B subunits induce thrombotic microangiopathy in Adamts13(-/-) mice. These results demonstrate the existence of a novel Stx B-induced lipid raft-dependen...Continue Reading

References

Feb 21, 1992·Cell·K G RothbergR G Anderson
Feb 1, 1989·The Journal of Cell Biology·J E Heuser, R G Anderson
Mar 5, 1998·The American Journal of Physiology·F B SchapiroS Grinstein
Nov 28, 2001·The Journal of Biological Chemistry·Anna M SoltykJames L Brunton
Feb 25, 2003·The Journal of Infectious Diseases·George L MulveyGlen D Armstrong
Apr 12, 2003·Arteriosclerosis, Thrombosis, and Vascular Biology·Philippe G FrankMichael P Lisanti
Sep 11, 2003·JAMA : the Journal of the American Medical Association·Amit X GargWilliam F Clark
Nov 24, 2004·Immunology·Tahir M RazzaqPanagiotis S Kabouridis
Mar 23, 2005·Lancet·Phillip I TarrWayne L Chandler
Aug 17, 2005·Journal of Thrombosis and Haemostasis : JTH·J A LópezC N Shrimpton
Oct 4, 2005·The Journal of Clinical Investigation·David G MottoDavid Ginsburg
Nov 30, 2007·Nature·Winfried RömerLudger Johannes
Dec 27, 2008·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Anna TarantaFrancesco Emma
Apr 29, 2009·The Journal of Cell Biology·Patrick LajoieIvan R Nabi
Jun 16, 2009·Nature Cell Biology·Carsten G HansenBenjamin J Nichols

❮ Previous
Next ❯

Citations

Aug 17, 2011·Seminars in Immunopathology·Victor W M van Hinsbergh
Jan 11, 2012·The Journal of Clinical Investigation·Tania N Petruzziello-PellegriniPhilip A Marsden
Jul 2, 2011·PloS One·Ramesh TatiDiana Karpman
Feb 22, 2012·PloS One·Karen M GallegosAlison A Weiss
Dec 4, 2012·Toxins·Chad L MayerDeborah J Stearns-Kurosawa
Aug 15, 2014·The New England Journal of Medicine·James N George, Carla M Nester
Sep 23, 2014·The Journal of Clinical Investigation·Qiuyu ZhuCharles J Lowenstein
Jul 7, 2012·Cellular and Molecular Life Sciences : CMLS·Andreas BauwensJohannes Müthing
Jan 15, 2015·Annual Review of Medicine·X Long Zheng
May 24, 2012·Seminars in Nephrology·David Motto
Apr 3, 2012·Experimental Cell Research·Marya ObeidatBarbara J Ballermann
Jul 17, 2013·Journal of Thrombosis and Haemostasis : JTH·K Vanhoorelbeke, S F De Meyer
Jul 17, 2013·Journal of Thrombosis and Haemostasis : JTH·X L Zheng
Jun 5, 2015·Hematology/oncology Clinics of North America·Lindsay Susan Keir
Nov 6, 2018·Journal of Atherosclerosis and Thrombosis·Yoko YoshidaMasaomi Nangaku
Dec 28, 2019·PloS One·R I KushakE F Grabowski
Jul 24, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ramesh TatiDiana Karpman
Jan 14, 2020·Journal of Medical Case Reports·B M D B BasnayakeR M B S S Mahanama
Apr 28, 2017·International Journal of Laboratory Hematology·K Kottke-Marchant
Oct 8, 2013·The Journal of Biological Chemistry·Nathan C LoJoel Moake

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood Clotting Disorders

Thrombophilia includes conditions with increased tendency for excessive blood clotting. Blood clotting occurs when the body has insufficient amounts of specialized proteins that make blood clot and stop bleeding. Here is the latest research on blood clotting disorders.

Caveolins & Signal Transduction

Caveolins are small proteins with a hairpin loop conformation that are located in the plasma membrane of various cell types where they bind cholesterol and interact with receptors essential for several signal transduction pathways. Here is the latest research.