Human serum amyloid P component protects against Escherichia coli O157:H7 Shiga toxin 2 in vivo: therapeutic implications for hemolytic-uremic syndrome.
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.
Armstrong
Glen D
GD
Department of Microbiology and Infectious Diseases, University of Calgary, Calgary, Canada. glen.armstrong@ucalgary.ca
Mulvey
George L
GL
Marcato
Paola
P
Griener
Thomas P
TP
Kahan
Melvyn C
MC
Tennent
Glenys A
GA
Sabin
Caroline A
CA
Chart
Henrik
H
Pepys
Mark B
MB
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D004195:Disease Models, Animal; D019453:Escherichia coli O157 / Q000737:chemistry / Q000472:pathogenicity*; D005260:Female; D006463:Hemolytic-Uremic Syndrome / Q000628:therapy*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008875:Middle Aged; D011485:Protein Binding / Q000187:drug effects; D000683:Serum Amyloid P-Component / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D022641:Shiga Toxin 2 / Q000097:blood / Q000378:metabolism*; D016019:Survival Analysis; D013997:Time Factors
D000683:Serum Amyloid P-Component; D022641:Shiga Toxin 2; D002118:Calcium