Document Detail


Quiescent complement in nonhuman primates during E coli Shiga toxin-induced hemolytic uremic syndrome and thrombotic microangiopathy.
MedLine Citation:
PMID:  23733336     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Enterohemorrhagic Escherichia coli (EHEC) produce ribosome-inactivating Shiga toxins (Stx1, Stx2) responsible for development of hemolytic uremic syndrome (HUS) and acute kidney injury (AKI). Some patients show complement activation during EHEC infection, raising the possibility of therapeutic targeting of complement for relief. Our juvenile nonhuman primate (Papio baboons) models of endotoxin-free Stx challenge exhibit full spectrum HUS, including thrombocytopenia, hemolytic anemia, and AKI with glomerular thrombotic microangiopathy. There were no significant increases in soluble terminal complement complex (C5b-9) levels after challenge with lethal Stx1 (n = 6) or Stx2 (n = 5) in plasma samples from T0 to euthanasia at 49.5 to 128 hours post-challenge. d-dimer and cell injury markers (HMGB1, histones) confirmed coagulopathy and cell injury. Thus, complement activation is not required for the development of thrombotic microangiopathy and HUS induced by EHEC Shiga toxins in these preclinical models, and benefits or risks of complement inhibition should be studied further for this infection.
Authors:
Benjamin C Lee; Chad L Mayer; Caitlin S Leibowitz; D J Stearns-Kurosawa; Shinichiro Kurosawa
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-06-03
Journal Detail:
Title:  Blood     Volume:  122     ISSN:  1528-0020     ISO Abbreviation:  Blood     Publication Date:  2013 Aug 
Date Detail:
Created Date:  2013-08-02     Completed Date:  2013-10-28     Revised Date:  2014-08-03    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  803-6     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Coagulation / physiology
Complement Activation / physiology
Complement System Proteins / metabolism,  physiology*
Disease Models, Animal
Fibrin Fibrinogen Degradation Products / analysis
Hemolytic-Uremic Syndrome / complications,  etiology,  immunology*
Papio
Primates
Shiga Toxin / pharmacology
Shiga-Toxigenic Escherichia coli / pathogenicity,  physiology
Thrombotic Microangiopathies / complications,  etiology,  immunology*,  metabolism
Time Factors
Grant Support
ID/Acronym/Agency:
P40OD010988/OD/NIH HHS; R01AI058107/AI/NIAID NIH HHS; R42AI062095/AI/NIAID NIH HHS; U01 AI1075386/AI/NIAID NIH HHS; U19 AI062629/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Fibrin Fibrinogen Degradation Products; 0/fibrin fragment D; 75757-64-1/Shiga Toxin; 9007-36-7/Complement System Proteins
Comments/Corrections

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