Differential tissue targeting and pathogenesis of verotoxins 1 and 2 in the mouse animal model
2002
receptor, globotriaosyl ceramide (Gb3). Although VT1 is slightly required for 50% lethality) was to increase, rather than reduce, more cytotoxic in vitro and binds Gb3 with higher affinity, VT2 is more toxic in mice and may be associated with greater pathology and further reduce the VT2 serum clearance rate. pathology in human infections. In this study we have compared Additional renal pathology was seen in VT2 adamantylGb3the biodistribution of iodine 125 ( 125 I)-VT1 and 125 I-VT2 versus treated mice. pathology in the mouse. Conclusions. The lung is a preferential (Gb3) “sink” for VT1, Methods. 125 I-VT1 whole-body autoradiography defined the which explains the relatively slower clearance of VT2 and subtissues targeted. VT1 and VT2 tissue distribution, clearance, sequent increased VT2 renal targeting and VT2 mortality in and tissue binding sites were compared. The effect of a soluble this animal model. receptor analogue, adamantylGb3, on VT2/Gb3 binding and in vivo pathology was assessed. Results. 125
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