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 AB₅-type exotoxins, consisting of a globotriaosylceramide (Gb₃)-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 Gb₃. In contrast, the investigation revealed that Stx2 binds to murine neutrophils by the classical Gb₃-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 ≤ 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.