Intravenous Shiga toxin 2 promotes enteritis and renal injury characterized by polymorphonuclear leukocyte infiltration and thrombosis in Dutch Belted rabbits.
Enterohemorrhagic Escherichia coli (EHEC) infection causes hemolytic uremic syndrome, a leading cause of acute renal failure in children. Dutch Belted (DB) rabbits are susceptible to EHEC-induced disease. Using real-time quantitative RT-PCR we measured the renal mRNA expression of cytokines and fibrinolytic factors in DB rabbits challenged with intravenous Shiga toxin 2 (Stx2) (1200 ng/kg). Group 1 rabbits received an incremental dose during an 8-day period whereas Group 2 rabbits received a single dose. Group 1 rabbits developed mild disease. In contrast, Group 2 rabbits developed severe diarrhea, higher levels of circulating polymorphonuclear leukocytes, increased mean platelet volume, and increased fibrinogen levels. Group 2 rabbits developed polymorphonuclear leukocyte infiltration in the intestine and kidney as well as glomerular congestion, luminal constriction, and mesangial glomerulonephropathy. These renal lesions were associated with up-regulation of interleukin-8 (P<0.006), plasminogen activator inhibitor-1 (P<0.04), and tissue plasminogen activator (P<0.05). Circulating Stx2 promoted dose-dependent enteritis and renal injury characterized by inflammation and impaired fibrinolysis leading to thrombosis.
García
Alexis
A
Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Ave 16-873, Cambridge, MA 02139, USA. agarcia@mit.edu
Marini
Robert P
RP
Catalfamo
James L
JL
Knox
Kimberly A
KA
Schauer
David B
DB
Rogers
Arlin B
AB
Fox
James G
JG
D000818:Animals; D004751:Enteritis / Q000209:etiology; D054324:Enterohemorrhagic Escherichia coli / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000382:microbiology / Q000473:pathology*; D006463:Hemolytic-Uremic Syndrome / Q000209:etiology / Q000382:microbiology / Q000473:pathology; D007668:Kidney / Q000737:chemistry / Q000473:pathology*; D009504:Neutrophils; D011817:Rabbits; D022641:Shiga Toxin 2 / Q000633:toxicity*; D013927:Thrombosis
D022641:Shiga Toxin 2