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-adrenergic agonists augment air pollution-induced IL-6 release and thrombosis
- Source :
- Journal of Clinical Investigation. July 1, 2014, Vol. 124 Issue 7, p2935, 12 p.
- Publication Year :
- 2014
-
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 [β.sub.2]-adrenergic receptor ([β.sub.2]AR) on murine alveolar macrophages and augment the release of IL-6. In mice, [β.sub.2]AR signaling promoted the development of a prothrombotic state that was sufficient to accelerate arterial thrombosis. In primary human alveolar macrophages, administration of a [β.sub.2]AR 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 [β.sub.2]AR on murine alveolar macrophages attenuated PM-induced IL-6 release and prothrombotic state. Furthermore, exogenous [β.sub.2]AR 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 [β.sub.2]AR signaling with metabolism, lung inflammation, and an enhanced susceptibility to thrombotic cardiovascular events.<br />Introduction Based on air pollution exposure estimates in the US from the late 1970s to the early 2000s, Pope et al. projected that a 10 µg/[m.sup.3] fall in the mean [...]
Details
- Language :
- English
- ISSN :
- 00219738
- Volume :
- 124
- Issue :
- 7
- Database :
- Gale General OneFile
- Journal :
- Journal of Clinical Investigation
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.376933975
- Full Text :
- https://doi.org/10.1172/JCI75157