title: A protein toxin from the sea anemone Phyllodiscus semoni targets the kidney and causes a severe renal injury with predominant glomerular endothelial damage.
abstract: 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.
authors.affiliation: Department of Nephrology, Nagoya University Graduate School of Medicine, Japan. mmizu@med.nagoya-u.ac.jp
authors.forename: Masashi
authors.initials: M
authors.lastname: Mizuno
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Nozaki
authors.forename: Nobuya
authors.initials: N
authors.lastname: Morine
authors.forename: Norihiko
authors.initials: N
authors.lastname: Suzuki
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nishikawa
authors.forename: B Paul
authors.initials: BP
authors.lastname: Morgan
authors.forename: Seiichi
authors.initials: S
authors.lastname: Matsuo
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D018958:CD55 Antigens / Q000032:analysis; D018957:CD59 Antigens / Q000032:analysis; D003064:Cnidarian Venoms / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D003167:Complement Activation / Q000187:drug effects; D003179:Complement C3b / Q000378:metabolism; D015938:Complement Membrane Attack Complex / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004727:Endothelium / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D005260:Female; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D012615:Sea Anemones / Q000737:chemistry*; D020539:Sequence Analysis, Protein; D014118:Toxins, Biological / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*
chemical_list: D018958:CD55 Antigens; D018957:CD59 Antigens; D003064:Cnidarian Venoms; D015938:Complement Membrane Attack Complex; D014118:Toxins, Biological; D003179:Complement C3b