Influence of inflammation and nitric oxide upon platelet aggregation following deposition of diesel exhaust particles in the airways
British Journal of Pharmacology
Wiley / British Pharmacological Society
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BACKGROUND AND PURPOSE: Exposure to nanoparticulate pollution has been implicated in platelet-driven thrombotic events such as myocardial infarction. Inflammation and impairment of nitric oxide (NO) bioavailability have been proposed as potential causative mechanisms. It is unclear, however, whether airways exposure to combustion-derived nanoparticles such as diesel exhaust particles (DEP) or carbon black (CB) can augment platelet aggregation in vivo and the underlying mechanisms remain undefined. We aimed to investigate the impact of acute lung exposure to DEP and CB upon platelet activation and the associated role of inflammation and endothelial-derived NO. EXPERIMENTAL APPROACH: DEP and CB were intratracheally instilled into wild-type (WT) and eNOS(-/-) mice and platelet aggregation was assessed in vivo using an established model of radiolabelled platelet thromboembolism. The underlying mechanisms were investigated by measuring inflammatory markers, NO metabolites and light transmission aggregometry. KEY RESULTS: Platelet aggregation in vivo was significantly enhanced in WT and eNOS(-/-) mice following acute airways exposure to DEP but not CB. CB exposure but not DEP, was associated with significant increases in pulmonary neutrophils and IL-6 levels in the bronchoalveolar lavage fluid and plasma of WT mice. Neither DEP nor CB affected plasma nitrate/nitrite concentration and DEP-induced human platelet aggregation was inhibited by an NO donor. CONCLUSIONS AND IMPLICATIONS: Pulmonary exposure to DEP and subsequent platelet activation may be implicated in the reported increased cardiovascular risk associated with exposure to airborne pollution independent of its impact on inflammation or NO bioavailability.
This work was supported by a Project Grant from the British Heart Foundation (PG/10/80/28605) awarded to M Emerson and T D Tetley.
This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record.
Published online 24 April 2017
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