Vascular ultrastructure and DNA fragmentation in swine infected with Shiga toxin-producing Escherichia coli.
Shiga toxins (Stx) produced by Escherichia coli cause systemic vascular damage that manifests as edema disease in swine and hemolytic uremic syndrome in humans. In vitro, Stx inhibit protein synthesis and, depending on circumstances, induce necrosis, apoptosis, or both. The mechanism of in vivo Stx-mediated vascular damage is not known. The ability of Stx to cause apoptosis of vasculature in vivo was studied in pigs with edema disease that was produced by oral inoculation with Stx-producing E. coli. Arterioles of ileum and brain were evaluated by terminal dUTP nick-end labeling (TUNEL) assay for DNA fragmentation in myocytes (10 infected pigs, 5 control pigs) and by transmission electron microscopy for ultrastructural changes characteristic of apoptosis (17 infected pigs, 8 control pigs). In comparison with controls, increased numbers of TUNEL-positive arterioles were detected in 6/10 (60%) subclinically affected pigs 14-15 days after inoculation. Ultrastructurally, lesions in myocytes consisted of lysis (necrosis), with cytoplasmic debris and nuclear fragments contained between intact basement membranes. Endothelial cell changes ranged from acute swelling to necrosis and detachment from basement membrane. Subclinically affected pigs (n = 14) tended to have changes predominantly in myocytes, whereas pigs with clinical illness (n = 3) more commonly had changes in endothelial cells. The arteriolar lesions and clinical signs of edema disease are attributed to the effects of Stx on vasculature. Therefore, our findings suggest that the Stx-induced arteriolar lesions seen in this study were primarily necrotic, not apoptotic. We suspect that necrosis was the principal cause of the DNA fragmentation detected.
Matise
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Veterinary Medical Research Institute, Iowa State University, Ames 50011, USA.
Sirinarumitr
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Bosworth
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Moon
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HW
D000818:Animals; D017209:Apoptosis; D001160:Arterioles / Q000473:pathology; D001808:Blood Vessels / Q000473:pathology*; D053938:DNA Fragmentation; D004487:Edema / Q000473:pathology / Q000662:veterinary*; D004927:Escherichia coli Infections / Q000473:pathology / Q000662:veterinary*; D020287:In Situ Nick-End Labeling / Q000662:veterinary; D008854:Microscopy, Electron / Q000662:veterinary; D022621:Shiga Toxin; D013552:Swine; D013553:Swine Diseases / Q000235:genetics* / Q000382:microbiology / Q000473:pathology*; D014652:Vascular Diseases / Q000473:pathology / Q000662:veterinary*
D022621:Shiga Toxin