A protein toxin from the sea anemone Phyllodiscus semoni targets the kidney and causes a severe renal injury with predominant glomerular endothelial damage
| Autor: | Nobuya Morine, Masatoshi Nozaki, Masashi Mizuno, Norihiko Suzuki, Seiichi Matsuo, Kazuhiro Nishikawa, B. Paul Morgan |
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| Rok vydání: | 2007 |
| Předmět: |
Pathology
medicine.medical_specialty food.ingredient Blotting Western Kidney Glomerulus Phyllodiscus CD59 Antigens Complement Membrane Attack Complex Biology Kidney Pathology and Forensic Medicine Mice food Cnidarian Venoms Sequence Analysis Protein medicine Animals Amino Acid Sequence Endothelium Rats Wistar Complement Activation Acute tubular necrosis Toxins Biological Mice Inbred BALB C CD55 Antigens Dose-Response Relationship Drug Glomerular basement membrane medicine.disease Immunohistochemistry Complement system Rats Microscopy Electron medicine.anatomical_structure Sea Anemones Renal pathology Mesangiolysis Complement C3b Electrophoresis Polyacrylamide Gel Female Complement membrane attack complex Protein Binding Regular Articles |
| Zdroj: | The American journal of pathology. 171(2) |
| ISSN: | 0002-9440 |
| Popis: | Envenomation by the sea anemone Phyllodiscus semoni causes fulminant dermatitis and, rarely, acute renal failure in humans. Here, we investigated whether the venom extracted from the nematocysts (PsTX-T) was nephrotoxic when administered intravenously in rats and whether PsTX-T induced activation of the complement system. Although small dose of PsTX-T induced acute tubular necrosis in rats resembling pathology seen in patients, kidneys displayed glomerular injury with glomerular endothelial damage, thrombus formation, mesangiolysis, and partial rupture of glomerular basement membrane, accompanied by severe tubular necrosis at 24 hours after administration of 0.03 mg of PsTX-T per animal, similar to the glomerular findings typical of severe hemolytic uremic syndrome. The early stage injury was accompanied by specific PsTX-T binding, massive complement C3b, and membrane attack complex deposition in glomeruli in the regions of injury and decreased glomerular expression of complement regulators. A pathogenic role for complement was confirmed by demonstrating that systemic complement inhibition reduced renal injury. The isolated nephrotoxic component, a 115-kd protein toxin (PsTX-115), was shown to cause identical renal pathology. The demonstration that PsTX-T and PsTX-115 were highly nephrotoxic acting via induction of complement activation suggests that inhibition of complement might be used to prevent acute renal damage following envenomation by P. semoni. |
| Databáze: | OpenAIRE |
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