Infecting mice with recombinant Ad5-BPI₂₃-Fcγ1 virus protects against systemic Escherichia coli challenge.
Infections caused by Gram-negative bacteria (GNB) are increasingly common and can result in significant mortality rates due to the development of sepsis. To examine the potential usage of a recombinant Ad5-BPI(23)-Fcγ1 virus as a biological treatment against systemic infection by GNB, a construct containing the human bactericidal/permeability increasing protein (BPI) gene, encoding the functional N terminus (amino acid residues 1-199) of human BPI, and the Fcγ1 gene, encoding the Fc segment of human immunoglobulin G1, was inserted into an adenovirus serotype 5 (Ad5) chromosome to produce a recombinant Ad5-BPI(23)-Fcγ1 virus. Human A549 cells in culture and BALB/c mice were infected with the recombinant Ad5-BPI(23)-Fcγ1 virus and BPI(23)-Fcγ1 expression was confirmed by Western blot analysis and ELISA. The concentrations of BPI(23)-Fcγ1 protein were 5.59 µg ml(-1) in vitro and 21.37 ng ml(-1) in vivo and it was observed that these concentrations were sufficient to decrease endotoxin concentrations while enhancing bactericidal activity. In addition, mice treated with the recombinant Ad5-BPI(23)-Fcγ1 virus had decreased levels of IL-1β and TNF-α and were protected from an E. coli O111 : B4 challenge. Our data support the concept that Ad5-mediated BPI(23)-Fcγ1 gene delivery could be used as an ancillary biological treatment in the management of infection caused by GNB.
Department of Immunology, Capital Medical University, Beijing, 100069, PR China.
Qingli
Q
Kong
Department of Immunology, Capital Medical University, Beijing, 100069, PR China.
Yanqiu
Y
Chen
Department of Immunology, Capital Medical University, Beijing, 100069, PR China.
Zhe
Z
Lv
Department of Immunology, Capital Medical University, Beijing, 100069, PR China.
Jun
J
Long
Laboratory Department, Capital Institute of Pediatrics, Beijing 100020, PR China.
Jing
J
Li
China Rehabilitation Research Centre, Beijing 100077, PR China.
Chen
C
Li
Department of Immunology, Capital Medical University, Beijing, 100069, PR China.
Yun
Y
Kang
Department of Immunology, Capital Medical University, Beijing, 100069, PR China.
Mingjie
M
Wen
Department of Immunology, Capital Medical University, Beijing, 100069, PR China.
Yunqing
Y
An
D000256:Adenoviridae / Q000235:genetics* / Q000472:pathogenicity; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics* / Q000378:metabolism; D001798:Blood Proteins / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000517:prevention & control; D004926:Escherichia coli / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000517:prevention & control*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics* / Q000378:metabolism; D007074:Immunoglobulin G / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D016896:Treatment Outcome
D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; C021623:bactericidal permeability increasing protein