ß2-Adrenergic agonists augment air pollution-induced IL-6 release and thrombosis.
J Clin Invest
; 124(7): 2935-46, 2014 Jul.
Article
en En
| MEDLINE
| ID: mdl-24865431
ABSTRACT
Acute exposure to particulate matter (PM) air pollution causes thrombotic cardiovascular events, leading to increased mortality rates; however, the link between PM and cardiovascular dysfunction is not completely understood. We have previously shown that the release of IL-6 from alveolar macrophages is required for a prothrombotic state and acceleration of thrombosis following exposure to PM. Here, we determined that PM exposure results in the systemic release of catecholamines, which engage the ß2-adrenergic receptor (ß2AR) on murine alveolar macrophages and augment the release of IL-6. In mice, ß2AR signaling promoted the development of a prothrombotic state that was sufficient to accelerate arterial thrombosis. In primary human alveolar macrophages, administration of a ß2AR agonist augmented IL-6 release, while the addition of a beta blocker inhibited PM-induced IL-6 release. Genetic loss or pharmacologic inhibition of the ß2AR on murine alveolar macrophages attenuated PM-induced IL-6 release and prothrombotic state. Furthermore, exogenous ß2AR agonist therapy further augmented these responses in alveolar macrophages through generation of mitochondrial ROS and subsequent increase of adenylyl cyclase activity. Together, these results link the activation of the sympathetic nervous system by ß2AR signaling with metabolism, lung inflammation, and an enhanced susceptibility to thrombotic cardiovascular events.
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1
Bases de datos:
MEDLINE
Asunto principal:
Trombosis
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Interleucina-6
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Material Particulado
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Agonistas de Receptores Adrenérgicos beta 2
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
J Clin Invest
Año:
2014
Tipo del documento:
Article