Abstract
Vibrio vulnificus, an opportunistic human pathogen causing wound infection and septicemia, produces 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 proteins were investigated. We found that native VVP and its derivative were able to act directly on many biologically 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 cascade 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 indispensable 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 language | English |
|---|---|
| Pages (from-to) | 959-966 |
| Number of pages | 8 |
| Journal | Microbiology and Immunology |
| Volume | 39 |
| Issue number | 12 |
| Publication status | Published - 1995 |
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Keywords
- Metalloprotease
- Proteinase inhibitor
- Vibrio vulnificus
ASJC Scopus subject areas
- Immunology and Microbiology(all)
- Microbiology (medical)
- Microbiology
Cite this
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. / Miyoshi, Shin-ichi; Narukawa, H.; Tomochika, K. I.; Shinoda, S.
In: Microbiology and Immunology, Vol. 39, No. 12, 1995, p. 959-966.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Actions of Vibrio vulnificus metalloprotease on human plasma proteinase- proteinase inhibitor systems
T2 - A comparative study of native protease with its derivative modified by polyethylene glycol
AU - Miyoshi, Shin-ichi
AU - Narukawa, H.
AU - Tomochika, K. I.
AU - Shinoda, S.
PY - 1995
Y1 - 1995
N2 - Vibrio vulnificus, an opportunistic human pathogen causing wound infection and septicemia, produces 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 proteins were investigated. We found that native VVP and its derivative were able to act directly on many biologically 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 cascade 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 indispensable 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.
AB - Vibrio vulnificus, an opportunistic human pathogen causing wound infection and septicemia, produces 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 proteins were investigated. We found that native VVP and its derivative were able to act directly on many biologically 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 cascade 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 indispensable 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.
KW - Metalloprotease
KW - Proteinase inhibitor
KW - Vibrio vulnificus
UR - http://www.scopus.com/inward/record.url?scp=0029595242&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029595242&partnerID=8YFLogxK
M3 - Article
C2 - 8789055
AN - SCOPUS:0029595242
VL - 39
SP - 959
EP - 966
JO - Microbiology and Immunology
JF - Microbiology and Immunology
SN - 0385-5600
IS - 12
ER -