Protection of mice from lethal endotoxemia by chimeric human BPI-Fcgamma1 gene delivery.
To evaluate the potentiality of applying gene therapy to endotoxemia in high-risk patients, we investigated the effects of transferring an adeno-associated virus serotype 2 (AAV2)-mediated BPI-Fcgamma1 gene on protecting mice from challenge of lethal endotoxin. The chimeric BPI-Fcgamma1 gene consists of two parts, one encods functional N-terminus (1 to 199 amino acidic residues) of human BPI, which is a bactericidal/permeability-increasing protein, and the other encodes Fc segment of human immunoglobulin G1 (Fcgamma1). Our results indicated that the target protein could be expressed and secreted into the serum of the gene-transferred mice. After lethal endotoxin challenge, the levels of endotoxin and TNF-alpha in the gene-transferred mice were decreased. The survival rate of the BPI-Fcgamma1 gene-transferred mice was markedly increased. Our data suggest that AAV2-mediated chimeric BPI-Fcgamma1 gene delivery can potentially be used clinically for the protection and treatment of endotoxemia and endotoxic shock in high-risk individuals.
Li
Chen
C
Department of Microbiology and Immunology, Capital University of Medical Sciences, Beijing, China.
Li
Jing
J
Lv
Zhe
Z
Guo
Xinghua
X
Chen
Qinghua
Q
Kong
Qingli
Q
An
Yunqing
Y
D000818:Animals; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D002460:Cell Line; D000229:Dependovirus / Q000235:genetics; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000139:chemically induced / Q000517:prevention & control*; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D006801:Humans; D008070:Lipopolysaccharides; D051379:Mice; D008807:Mice, Inbred BALB C; D011506:Proteins / Q000235:genetics*; D017452:Receptors, IgG / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D015996:Survival Rate
D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D008070:Lipopolysaccharides; D011506:Proteins; D017452:Receptors, IgG; D011993:Recombinant Fusion Proteins; C021623:bactericidal permeability increasing protein