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PMID: 15772169 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Human alpha-defensins neutralize anthrax lethal toxin and protect against its fatal consequences.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 102 ·No. 13 ·2005-03-29 ·Pages 4830-5

Kim C, Gajendran N, Mittrücker HW, Weiwad M, Song YH, Hurwitz R, Wilmanns M, Fischer G, Kaufmann SH

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.

MeSH Terms
Animals Antigens, Bacterial Bacterial Toxins/antagonists & inhibitors Female Furin/antagonists & inhibitors Humans Kinetics MAP Kinase Kinase 3/metabolism Macrophages/drug effects,metabolism Matrix Metalloproteinase Inhibitors Mice Mice, Inbred BALB C Signal Transduction/drug effects Spores, Bacterial/drug effects Survival Analysis Tetrazolium Salts Thiazoles alpha-Defensins/metabolism,pharmacology
Chemicals
Antigens, Bacterial Bacterial Toxins Matrix Metalloproteinase Inhibitors Tetrazolium Salts Thiazoles alpha-Defensins anthrax toxin human neutrophil peptide 1 MAP Kinase Kinase 3 Furin thiazolyl blue
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Kim Chun
Department of Immunology, Max Planck Institute for Infection Biology, Schumannstrasse 21-22, D-10117 Berlin, Germany.
Gajendran Nadesan
Mittrücker Hans-Willi
Weiwad Matthias
Song Young-Hwa
Hurwitz Robert
Wilmanns Matthias
Fischer Gunter
Kaufmann Stefan H E
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0500508102
Published
2005-03-29
Epub
2005-00-16
Pages
4830-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC555714
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.0500508102 PMC Full Text View journal details
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