Platelet-activating factor and Escherichia coliO157:H7 infections.
The role of platelet-activating factor (PAF), a phospholipid inflammatory mediator, in Escherichia coli O157:H7-associated hemolytic uremic syndrome (HUS) is unknown. PAF is synthesized by diverse cells and is degraded by PAF-acetylhydrolase (PAF-AH). Deficient PAF-AH activity results from a G-->T transversion at position 994 of exon 9. We examined children infected with E. coliO157:H7 to determine if PAF levels or the PAF-AH ( G994T) mutation reflects the risk of developing HUS. Plasma PAF concentrations were determined using chloroform/methanol extraction, thin layer chromatography purification, and scintillation proximity assay in 10 patients with uncomplicated infection (UI), 10 infected patients who subsequently developed HUS (pre-HUS), 5 HUS patients, and 8 healthy controls. The PAF-AH ( G994T) allele frequency was determined in 52 UI children, 15 with HUS, and 11 controls. Wilcoxon rank sum tests were performed to test differences in location (median) of pairs of groups. PAF levels were higher in the UI ( P=0.04) and pre-HUS ( P=0.01) groups than in healthy controls. No subject had the PAF-AH ( G994T) allele. Thus, elevated plasma PAF levels occur in E. coliO157:H7-infected children, even without HUS, but diminish when HUS develops. The PAF-AH ( G994T) allele does not contribute to the risk of developing HUS.
Smith
Jodi M
JM
Division of Nephrology, Children's Hospital and Regional Medical Center, Department of Pediatrics, University of Washington, Seattle, Washington, USA.
Jones
Falaah
F
Ciol
Marcia A
MA
Jelacic
Srdjan
S
Boster
Daniel R
DR
Watkins
Sandra L
SL
Williams
Glyn D
GD
Tarr
Phillip I
PI
Henderson
William R
WR
D001772:Blood Cell Count; D002675:Child, Preschool; D004247:DNA / Q000032:analysis; D004927:Escherichia coli Infections / Q000097:blood*; D019453:Escherichia coli O157; D005260:Female; D005838:Genotype; D006463:Hemolytic-Uremic Syndrome / Q000453:epidemiology; D006801:Humans; D016015:Logistic Models; D008297:Male; D009154:Mutation / Q000235:genetics; D010972:Platelet Activating Factor / Q000235:genetics / Q000378:metabolism*; D011446:Prospective Studies; D018570:Risk Assessment
D010972:Platelet Activating Factor; D004247:DNA