Effects of Vibrio vulnificus metalloprotease on the capillaries: Pathological actions and inactivation by α-macroglobulin

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Vibrio vulnificus is an opportunistic human pathogen causing wound infection and septicemia, characterized by hemorrhagic and edematous damage to the skin of limbs. When injected into the dorsal skin, an extracellular metalloprotease from this vibrio (V. vulnificus protease: VVP) enhanced the vascular permeability through activation of the Hageman factor-plasma kallikrein-kinin cascade and/or stimulation of exocytotic histamine release. Additionally, VVP caused the hemorrhagic skin lesion through disorganization of the vascular basement membrane layer due to specific degradation of type IV collagen, which is known to form the backbone structure of the basement membrane. However, injected VVP was quickly inactivated by a plasma glycoprotein, α-macroglobulin, at a molar ratio of 1 : 1. This glycoprotein was leaked from the capillaries by the actions of VVP, which resulted in in situ inactivation by physical entrapment. When VVP (45000 Da) was incubated at 37°C, a 35000 Da fragment was generated by the autocatalytic removal of a 10000Da C-terminal polypeptide. This N-terminal fragment showed significant proteolytic activity, however, because of a markedly decreased affinity to the protein substrates, its permeability-enhancing and hemorrhagic activity was reduced to less than 50%. These findings indicate that the C-terminal polypeptide is not essential for but promotes skin reactions caused by VVP.

Original languageEnglish
Pages (from-to)1149-1157
Number of pages9
JournalYakugaku Zasshi
Issue number11
Publication statusPublished - 2000


  • Hemorrhage
  • Histamine
  • Kallikrein-kinin
  • Metalloprotease
  • Vibrio vulnificus
  • α-macroglob ulin

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science


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