Actions of Vibrio vulnificus Metalloprotease on Human Plasma Proteinase-Proteinase Inhibitor Systems: A Comparative Study of Native Protease with Its Derivative Modified by Polyethylene Glycol

Shin ichi Miyoshi, Hitoshi Narukawa, Ken ichi Tomochika, Sumio Shinoda

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Vibrio vulnificus, an opportunistic human pathogen causing wound infection and septicemia, pro-duces a metalloprotease (VVP) which is suspected to be a virulent determinant. The interactions of VVP, as well as its derivative (PEG1-VVP) modified with polyethylene glycol, with a variety of human plasma pro-teins were investigated. We found that native VVP and its derivative were able to act directly on many bio-logically important human plasma proteins even in the presence of α-macroglobulin, the sole plasma inhibitor of native VVP. The activities of both classical and alternative pathways of the complement cas-cade system were drastically abolished by incubation with either VVP. Furthermore, these proteases rapidly digested the Aα-chain of human fibrinogen into fragment(s) with no clotting ability. Therefore both VVPs are thought to function as a fibrinogenolytic enzyme, causing delay of the coagulation reaction. VVP and PEG1-VVP were also shown to destroy plasma proteinase inhibitors including α1-proteinase inhibitor, a major inhibitor in human plasma. Because endogenous proteolytic enzymes and their inhibitors are indis-pensable in maintaining physiological homeostasis, these findings suggest that VVP (and PEG1-VVP) may cause an imbalance of human plasma proteinase-proteinase inhibitor systems, thus eliciting an immunocompromised state in the host and facilitating the development of a systemic V. vulnificus infection such as septicemia.

Original languageEnglish
Pages (from-to)959-966
Number of pages8
JournalMICROBIOLOGY and IMMUNOLOGY
Volume39
Issue number12
DOIs
Publication statusPublished - Jan 1 1995

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Keywords

  • Metalloprotease
  • Proteinase inhibitor
  • Vibrio vulnificus

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Virology

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