Differential binding of Shiga toxin 2 to human and murine neutrophils.
Shiga toxins (Stx1 and Stx2) are responsible for initiating haemolytic uraemic syndrome, a serious extraintestinal complication caused by enterohaemorrhagic Escherichia coli O157 : H7 infection in humans. Shiga toxins are classical AB(5)-type exotoxins, consisting of a globotriaosylceramide (Gb(3))-binding B subunit pentamer and an enzymic A subunit. It is demonstrated in this study that Stx2 binds to human neutrophils by a non-classical mechanism that is independent of Gb(3). In contrast, the investigation revealed that Stx2 binds to murine neutrophils by the classical Gb(3)-dependent mechanism. Moreover, whereas the human serum amyloid P (HuSAP) component inhibited Stx2 binding to murine neutrophils, HuSAP increased Stx2 binding to human neutrophils by 84.2 % (P< or =0.002, Student's t-test). These observations may explain why HuSAP protects mice from the lethal effects of Stx2, whereas there is no indication that HuSAP plays a similar protective role in humans infected by E. coli O157 : H7.
Griener
Thomas P
TP
Department of Microbiology and Infectious Diseases, University of Calgary Health Sciences Centre, Calgary, Alberta T2N 4N1, Canada.
Mulvey
George L
GL
Department of Microbiology and Infectious Diseases, University of Calgary Health Sciences Centre, Calgary, Alberta T2N 4N1, Canada.
Marcato
Paola
P
Department of Microbiology and Immunology, Sir Charles Tupper Medical Building, Dalhousie University, Halifax, Nova Scotia B3H 1X5, Canada.
Armstrong
Glen D
GD
Department of Microbiology and Infectious Diseases, University of Calgary Health Sciences Centre, Calgary, Alberta T2N 4N1, Canada.
D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D051379:Mice; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism*; D000683:Serum Amyloid P-Component / Q000502:physiology*; D022641:Shiga Toxin 2 / Q000378:metabolism* / Q000633:toxicity; D014281:Trihexosylceramides / Q000378:metabolism*
D000683:Serum Amyloid P-Component; D022641:Shiga Toxin 2; D014281:Trihexosylceramides; C018549:globotriaosylceramide