|
|
Prepublished online as a Blood First Edition Paper on September 22, 2003; DOI 10.1182/blood-2003-02-0660.
Submitted March 3, 2003
Accepted December 31, 1969
Protection from endotoxemia by adenoviral-mediated gene transfer of human bactericidal/permeability-increasing protein
Scott Alexander, Jonathan Bramson, Ronan Foley, and Zhou Xing*
Department of Pathology and Molecular Medicine, and Infectious Diseases Division, Centre for Gene Therapeutics, McMaster University, Hamilton, ON, Canada
* Corresponding author; email: xingz{at}mcmaster.ca.
Sepsis represents a growing concern in high-risk patients and there has been a lack of effective preventives and therapies. Bacterial/Permeability Increasing protein (BPI) is a human neutrophil granule-associated defense molecule specific for Gram negative bacteria and their products. To develop a BPI-transgene-based prophylactic or therapeutic modality, we have developed a recombinant, replication-deficient adenoviral vector expressing full-length human BPI protein (AdhBPI). The expression of BPI is under control of a murine CMV promoter. Using in vitro and in vivo systems, AdhBPI-mediated gene transfer led to extracellular secretion of BPI protein, which effectively neutralized endotoxin (LPS) and markedly reduced the production of proinflammatory cytokines TNF- and MIP-2 by freshly isolated murine alveolar macrophages. By using a mouse model of non-lethal sepsis elicited with LPS, we demonstrated that in vivo gene transfer of BPI was able to markedly inhibit the effect of a large dose of LPS on cytokine responses when injected intra-peritoneally. Furthermore, such in vivo BPI gene transfer also improved the survival of mice suffering from lethal septic shock elicited by intra-peritoneal injection of D-galactosamine and LPS. Thus, our results suggest that human BPI gene transfer vector has the potential to be used as a therapeutic agent for septic conditions.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
T. Gautier, A. Klein, V. Deckert, C. Desrumaux, N. Ogier, A.-L. Sberna, C. Paul, N. Le Guern, A. Athias, T. Montange, et al.
Effect of Plasma Phospholipid Transfer Protein Deficiency on Lethal Endotoxemia in Mice
J. Biol. Chem.,
July 4, 2008;
283(27):
18702 - 18710.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Chen, C. Li, Y. Guan, Q. Kong, C. Li, X. Guo, Q. Chen, X. Jing, Z. Lv, and Y. An
Protection of Mice from Lethal Escherichia coli Infection by Chimeric Human Bactericidal/Permeability-Increasing Protein and Immunoglobulin G1 Fc Gene Delivery
Antimicrob. Agents Chemother.,
February 1, 2007;
51(2):
724 - 731.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. S. D. Weber, S. A. Madsen-Bouterse, G. J. M. Rosa, S. Sipkovsky, X. Ren, P. E. Almeida, R. Kruska, R. G. Halgren, J. L. Barrick, and J. L. Burton
Analysis of the bovine neutrophil transcriptome during glucocorticoid treatment
Physiol Genomics,
December 13, 2006;
28(1):
97 - 112.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Fujita, K.-i. Seino, K. Sato, Y. Sato, K. Eizumi, N. Yamashita, M. Taniguchi, and K. Sato
Regulatory dendritic cells act as regulators of acute lethal systemic inflammatory response
Blood,
May 1, 2006;
107(9):
3656 - 3664.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Levy
Antimicrobial proteins and peptides: anti-infective molecules of mammalian leukocytes
J. Leukoc. Biol.,
November 1, 2004;
76(5):
909 - 925.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
