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

Chun Kim, Nadesan Gajendran, Hans Willi Mittrücker, Matthias Weiwad, Young Hwa Song, Robert Hurwitz, Matthias Wilmanns, Gunter Fischer, Stefan H.E. Kaufmann*

*Korrespondierende/r Autor/-in für diese Arbeit
119 Zitate (Scopus)

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 α-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.

OriginalspracheEnglisch
ZeitschriftProceedings of the National Academy of Sciences of the United States of America
Jahrgang102
Ausgabenummer13
Seiten (von - bis)4830-4835
Seitenumfang6
ISSN0027-8424
DOIs
PublikationsstatusVeröffentlicht - 29.03.2005

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