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• W2113448462 startingPage "625" @default.
• W2113448462 abstract "The filamentous fungus Aspergillus fumigatus produces a variety of enzymes and toxins that may facilitate fungal colonization of tissue and evasion of the host immune response. One such toxin, fumagillin, was investigated for its ability to inhibit the action of neutrophils, which are a central component of the innate immune response to microbial infection. Neutrophils exposed to 2 microg fumagillin ml(-1) for 25 min showed a significantly reduced ability to kill yeast cells (P<0.02), to phagocytose conidia of A. fumigatus (P<0.023) and to consume oxygen (P<0.032). The ability of neutrophils to generate superoxide is dependent upon the action of a functional NADPH oxidase complex which is composed of cytosolic (p40phox, p47phox, p67phox, Rac2) and membrane (gp91phox) proteins. Exposure of neutrophils to fumagillin inhibited the formation of the NADPH oxidase complex by blocking the translocation of p47phox from the cytosolic to the membrane fraction (P=0.02). In addition to the production of superoxide, neutrophils also undergo degranulation, which leads to the release of proteolytic enzymes that contribute to the microbicidal activity of the cell. Fumagillin-treated neutrophils showed reduced degranulation as evidenced by lower myeloperoxidase activity (P<0.019). Fumagillin-treated cells demonstrated reduced levels of F-actin, thus indicating that retarding the formation of F-actin may contribute to the inhibition of the structural rearrangements required in the activated neutrophil. This work indicates that fumagillin may contribute to reducing the local immune response by altering the activity of neutrophils and thus facilitate the continued persistence and growth of A. fumigatus in the host." @default.
• W2113448462 created "2016-06-24" @default.
• W2113448462 creator A5020032485 @default.
• W2113448462 creator A5043776406 @default.
• W2113448462 creator A5062384147 @default.
• W2113448462 date "2010-06-01" @default.
• W2113448462 modified "2023-09-26" @default.
• W2113448462 title "Inhibition of neutrophil function following exposure to the Aspergillus fumigatus toxin fumagillin" @default.
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• W2113448462 doi "https://doi.org/10.1099/jmm.0.018192-0" @default.
• W2113448462 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20203215" @default.
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