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Human alpha-defensins neutralize anthrax lethal toxin and protect against its fatal consequences.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2005 Mar 29; Vol. 102 (13), pp. 4830-5. Date of Electronic Publication: 2005 Mar 16. - Publication Year :
- 2005
-
Abstract
- Anthrax caused by Bacillus anthracis represents a major bioterroristic threat. B. anthracis produces lethal toxin (LeTx), a combination of lethal factor (LF) and protective antigen that plays a major role in anthrax pathogenesis. We demonstrate that human neutrophil alpha-defensins are potent inhibitors of LF. The inhibition of LF by human neutrophil protein (HNP-1) was noncompetitive. HNP-1 inhibited cleavage of a mitogen-activated protein kinase kinase and restored impaired mitogen-activated protein kinase signaling in LeTx-treated macrophages. HNP-1 rescued murine macrophages from B. anthracis-induced cytotoxicity, and in vivo treatment with HNP-1-3 protected mice against the fatal consequences of LeTx.
- Subjects :
- Animals
Antigens, Bacterial
Female
Furin antagonists & inhibitors
Humans
Kinetics
MAP Kinase Kinase 3 metabolism
Macrophages metabolism
Matrix Metalloproteinase Inhibitors
Mice
Mice, Inbred BALB C
Spores, Bacterial drug effects
Survival Analysis
Tetrazolium Salts
Thiazoles
alpha-Defensins metabolism
Bacterial Toxins antagonists & inhibitors
Macrophages drug effects
Signal Transduction drug effects
alpha-Defensins pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0027-8424
- Volume :
- 102
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 15772169
- Full Text :
- https://doi.org/10.1073/pnas.0500508102