| Description |
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Background: Hemolytic uremic syndrome (HUS) leading to acute kidney
failure, is a condition linked to the production of primarily Shiga toxin 2 (Stx2) by
some E. coli serotypes. We have previously shown that Stx2 A subunit-specific human
monoclonal antibody (HuMAb) 5C12, and B subunit-specific HuMAb 5H8 inhibit cultured
cell death, and ... read moreprotect mice and piglets from fatal Stx2-intoxication. We have also
shown that 5H8 blocks binding of Stx2 to its cell-surface receptor globotriaosyl
ceramide (Gb3), whereas Stx2 when complexed with 5C12 binds Gb3 with higher affinity
than Stx2. The mechanism by which 5C12 neutralizes Stx2 in vitro involves trapping of
Stx2 in the recycling endosomes and releasing it into the extracellular environment.
Because of the clinical implications associated with the formation of Stx2/antibody
complexes and the potential for trapping and clearance through a severely damaged
kidney associated with HUS, we investigated the likely site(s) of Stx2/antibody
localization and clearance in intoxicated mice treated with antibody or
placebo.
Keywords: Shiga toxin, Radiolabel, Antibody, Toxin elimination, Toxin
concentration, Pharmacokinetic, Human monoclonal antibody.
Springer Open.read less
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| Citation |
- Sheoran, Abhineet, Kwang-il Jeong, Jean Mukherjee, Anthony
Wiffin, Pradeep Singh, and Saul Tzipori. "Biodistribution and elimination kinetics of
systemic Stx2 by the Stx2A and Stx2B subunit-specific human monoclonal antibodies in
mice." BMC Immunology 13, no. 1 (12, 2012): 1-8.
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