Renal prostacyclin biosynthesis in a baboon model of Shiga toxin mediated hemolytic uremic syndrome.
OBJECTIVE
Shiga toxin (Stx) and lipopolysaccharide (LPS) both participate in the pathogenesis of post-diarrheal (D+) hemolytic uremic syndrome (HUS), but little is known about factors that modulate the host response to these toxins. Prostacyclin (PGI(2)) is a potent renal vasodilator and inhibitor of platelet aggregation and adhesion. An inability to produce PGI(2) in response to endothelial cell injury could drive the pathogenic cascade. We therefore used a baboon model of HUS to measure PGI(2 )production following the administration of Stx and LPS.


METHODS
Shiga toxin-1 (Stx-1), with and without LPS, was administered intravenously to baboons in various doses and schedules. 6-keto-PGF(1)alpha, the stable metabolite of PGI(2), was measured by ELISA in the plasma and urine.


RESULTS
Plasma concentrations did not change significantly. Urine values increased significantly in some groups, but not in others, and HUS developed both in animals that did and did not exhibit a significant increase in urinary PGI(2) production.


CONCLUSIONS
Renal PGI(2) biosynthesis appears to be affected by the dose and rate of Stx administration, and the timing of LPS infusion. PGI(2) does not protect our primate model from developing HUS.
Siegler
Richard L
RL
Department of Pediatrics, Division of Nephrology and Hypertension, 30 N. 1900 E, #28422, Salt Lake City, UT 84132-2204, USA. dick.siegler@hsc.utah.edu
Pysher
Theodore J
TJ
Tesh
Vernon L
VL
Taylor
Fletcher B
FB
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood / Q000652:urine; D000818:Animals; D004195:Disease Models, Animal; D011464:Epoprostenol / Q000096:biosynthesis*; D006463:Hemolytic-Uremic Syndrome / Q000209:etiology / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000633:toxicity; D010215:Papio; D022622:Shiga Toxin 1 / Q000008:administration & dosage / Q000633:toxicity
D008070:Lipopolysaccharides; D022622:Shiga Toxin 1; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol