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Cyclic AMP-mediated suppression of neutrophil extracellular trap formation and
apoptosis by the Bordetella pertussis adenylate cyclase toxin
#MMPMID25287922
Eby JC
; Gray MC
; Hewlett EL
Infect Immun
2014[Dec]; 82
(12
): 5256-69
PMID25287922
show ga
The adenylate cyclase toxin (ACT) of Bordetella pertussis intoxicates target
cells by generating supraphysiologic levels of intracellular cyclic AMP (cAMP).
Since ACT kills macrophages rapidly and potently, we asked whether ACT would also
kill neutrophils. In fact, ACT prolongs the neutrophil life span by inhibiting
constitutive apoptosis and preventing apoptosis induced by exposure to live B.
pertussis. Imaging of B. pertussis-exposed neutrophils revealed that B. pertussis
lacking ACT induces formation of neutrophil extracellular traps (NETs), whereas
wild-type B. pertussis does not, suggesting that ACT suppresses NET formation.
Indeed, ACT inhibits formation of NETs by generating cAMP and consequently
inhibiting the oxidative burst. Convalescent-phase serum from humans following
clinical pertussis blocks the ACT-mediated suppression of NET formation. These
studies provide novel insight into the phagocyte impotence caused by ACT, which
not only impairs neutrophil function but also inhibits death of neutrophils by
apoptosis and NETosis.
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