Human serum amyloid P component protects against Escherichia coli O157:H7 shiga toxin 2 in vivo: Therapeutic implications for hemolytic-uremic syndrome

Glen D. Armstrong*, George L. Mulvey, Paola Marcato, Thomas P. Griener, Melvyn C. Kahan, Glenys A. Tennent, Caroline A. Sabin, Henrik Chart, Mark B. Pepys

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)

Abstract

Shiga toxin (Stx) 2 causes hemolytic-uremic syndrome (HUS), an intractable and often fatal complication of enterohemorrhagic Escherichia coli O157:H7 infection. Here, we show that serum amyloid P component (SAP), a normal human plasma protein, specifically protects mice against the lethal toxicity of Stx2, both when injected into wild-type mice and when expressed transgenically; in the presence of human SAP, there was greatly reduced in vivo localization of Stx2 to the kidneys, suggesting a possible mechanism of protection. In humans, circulating SAP concentrations did not differ between patients with suspected enterohemorrhagic E. coli infection with antibodies to E. coli O157:H7 lipopolysaccharide and those without antibodies or between patients with HUS and those without it. However, the potent protection conferred by human SAP in the mouse model suggests that infusion of supplemental SAP may be a useful novel therapeutic approach to the treatment of this devastating condition.

Original languageEnglish
Pages (from-to)1120-1124
Number of pages5
JournalJournal of Infectious Diseases
Volume193
Issue number8
DOIs
Publication statusPublished - 15 Apr 2006

Bibliographical note

Funding Information:
Financial support: Canadian Institutes for Health Research (operating grant MWS 56081 to G.D.A. and doctoral scholarship to P.M.); Canadian Bacterial Diseases Network (operating grant VP 17 to G.D.A.); Alberta Heritage Foundation for Medical Research (doctoral scholarship to P.M.); UK Medical Research Council Programme (grant G97900510 to M.B.P.).

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