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, Hitoshi
AU - Tomochika, Ken ichi
AU - Shinoda, Sumio
PY - 1995/1/1
Y1 - 1995/1/1
N2 - 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.
AB - 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.
KW - Metalloprotease
KW - Proteinase inhibitor
KW - Vibrio vulnificus
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U2 - 10.1111/j.1348-0421.1995.tb03299.x
DO - 10.1111/j.1348-0421.1995.tb03299.x
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 -