Human alpha-defensins neutralize anthrax lethal toxin and protect against its fatal consequences
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Human alpha-defensins neutralize anthrax lethal toxin and protect against its fatal consequences. / Kim, Chun; Gajendran, Nadesan; Mittrücker, Hans-Willi; Weiwad, Matthias; Song, Young-Hwa; Hurwitz, Robert; Wilmanns, Matthias; Fischer, Gunter; Kaufmann, Stefan H E.
In: P NATL ACAD SCI USA, Vol. 102, No. 13, 29.03.2005, p. 4830-5.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Human alpha-defensins neutralize anthrax lethal toxin and protect against its fatal consequences
AU - Kim, Chun
AU - Gajendran, Nadesan
AU - Mittrücker, Hans-Willi
AU - Weiwad, Matthias
AU - Song, Young-Hwa
AU - Hurwitz, Robert
AU - Wilmanns, Matthias
AU - Fischer, Gunter
AU - Kaufmann, Stefan H E
PY - 2005/3/29
Y1 - 2005/3/29
N2 - 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.
AB - 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.
KW - Animals
KW - Antigens, Bacterial
KW - Bacterial Toxins
KW - Female
KW - Furin
KW - Humans
KW - Kinetics
KW - MAP Kinase Kinase 3
KW - Macrophages
KW - Matrix Metalloproteinase Inhibitors
KW - Mice
KW - Mice, Inbred BALB C
KW - Signal Transduction
KW - Spores, Bacterial
KW - Survival Analysis
KW - Tetrazolium Salts
KW - Thiazoles
KW - alpha-Defensins
U2 - 10.1073/pnas.0500508102
DO - 10.1073/pnas.0500508102
M3 - SCORING: Journal article
C2 - 15772169
VL - 102
SP - 4830
EP - 4835
JO - P NATL ACAD SCI USA
JF - P NATL ACAD SCI USA
SN - 0027-8424
IS - 13
ER -