Abstract |
To obtain better insight into the pathogenesis of verotoxin-producing Escherichia coli-associated diseases, in this study, we explored the effect of verotoxin 2 (VT2) on coagulation in an animal model. After being given VT2 (50 ng/kg, lethal dose), C57BL/6 mice showed progressively increasing expression of TF mRNA in the kidney and brain and elevated plasma levels of thrombin-antithrombin III complex (TAT), normotest, fibrinogen, and PAI-1 paralleling the disease course over 24 hours; platelet counts were decreased at 48 hours with hemorrhage in the kidney and brain. Co-administration of lipopolysaccharide (LPS, 0.5 mg/kg) with VT2 (50 ng/kg) exhibited more prominant and/or prolonged increase in not only expression of TF and PAI-1 mRNAs in the kidney and brain but also plasma levels of TAT, fibrinogen, and PAI-1 and was associated with more remarkable hemorrhage in the tissues. Although VT2 (5 ng/kg) was not a lethal dose, co-administration of LPS (0.5 mg/kg) with VT2 (5 ng/kg) enhanced the susceptibility to VT2, resulting in more prolonged elevation of TAT levels during the first 24 hours than that in the LPS group and a second elevation at 72 hours, followed by death. Plasma IL-1beta level reached a maximum at 24 hours after VT2 (50 ng/kg) injection prior to the increase in TAT levels, whereas the increase in TNFalpha level immediately after injection was associated with the increase in PAI-1 mRNA. These observations indicate that the activation of coagulation by VT2 may occur through a mechanism different from that used by LPS, since plasma TAT levels rose in the mice immediately after LPS injection and returned to normal over 36 hours.
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Authors | J Sugatani, T Igarashi, M Munakata, Y Komiyama, H Takahashi, N Komiyama, T Maeda, T Takeda, M Miwa |
Journal | Thrombosis research
(Thromb Res)
Vol. 100
Issue 1
Pg. 61-72
(Oct 01 2000)
ISSN: 0049-3848 [Print] United States |
PMID | 11053618
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Cytokines
- Lipopolysaccharides
- Plasminogen Activator Inhibitor 1
- RNA, Messenger
- Shiga Toxin 2
- antithrombin III-protease complex
- Antithrombin III
- Fibrinogen
- Thromboplastin
- Peptide Hydrolases
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Topics |
- Animals
- Antithrombin III
(drug effects)
- Blood Coagulation
(drug effects)
- Blood Coagulation Tests
- Brain
(drug effects, metabolism, pathology)
- Cytokines
(blood, drug effects)
- Dose-Response Relationship, Drug
- Drug Therapy, Combination
- Fibrinogen
(drug effects, metabolism)
- Hemorrhage
(chemically induced, pathology)
- Intracranial Hemorrhages
(chemically induced, pathology)
- Kidney
(drug effects, metabolism, pathology)
- Lipopolysaccharides
(pharmacology, toxicity)
- Male
- Mice
- Mice, Inbred C57BL
(blood)
- Models, Animal
- Neutrophils
(cytology)
- Peptide Hydrolases
(drug effects)
- Plasminogen Activator Inhibitor 1
(blood, genetics)
- Platelet Count
- RNA, Messenger
(metabolism)
- Shiga Toxin 2
(pharmacology, toxicity)
- Shock
(chemically induced)
- Thromboplastin
(genetics)
- Time Factors
- Tissue Distribution
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