Comparative analysis of the abilities of Shiga toxins 1 and 2 to bind to and influence neutrophil apoptosis.
Hemolytic-uremic syndrome (HUS), the life-threatening complication following infection by the intestinal pathogen Escherichia coli O157:H7, is due to the ability of the pathogen to produce toxins in the Shiga toxin (Stx) family. Activated neutrophils are observed in HUS patients, yet it is unclear whether Stx exerts a direct effect on neutrophils or whether the toxin acts indirectly. The effect of Stx1 and Stx2 on human neutrophils was examined. Neither Stx1 nor Stx2 altered the rate of neutrophil apoptosis. Minimal binding of either toxin to neutrophils was observed, and the toxin was easily eluted from the cells. Stx1 and Stx2 were found to circulate in the plasma of mice following intravenous injection, and both toxins were cleared rapidly from the blood. Together these results suggest that neither Stx1 nor Stx2 interacts directly with neutrophils.
Flagler
Michael J
MJ
Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati, Cincinnati, OH 45267, USA.
Strasser
Jane E
JE
Chalk
Claudia L
CL
Weiss
Alison A
AA
D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D009504:Neutrophils / Q000166:cytology* / Q000378:metabolism*; D011485:Protein Binding; D022622:Shiga Toxin 1 / Q000097:blood / Q000378:metabolism* / Q000633:toxicity; D022641:Shiga Toxin 2 / Q000097:blood / Q000378:metabolism* / Q000633:toxicity
D022622:Shiga Toxin 1; D022641:Shiga Toxin 2