Diesel Exhaust Particles in Lung Acutely Enhance Experimental Peripheral Thrombosis

Abstract

Background-Pollution by particulates has consistently been associated with increased cardiovascular morbidity and mortality, but a plausible biological basis for this association is lacking. Methods and Results-Diesel exhaust particles (DEPs) were instilled into the trachea of hamsters, and blood platelet activation, experimental thrombosis, and lung inflammation were studied. Doses of 5 to 500 g of DEPs per animal induced neutrophil influx into the bronchoalveolar lavage fluid with elevation of protein and histamine but without lactate dehydrogenase release. The same doses enhanced experimental arterial and venous platelet rich-thrombus formation in vivo. Blood samples taken from hamsters 30 and 60 minutes after instillation of 50 g of DEPs yielded accelerated aperture closure (ie, platelet activation) ex vivo, when analyzed in the Platelet Function Analyser (PFA-100).The direct addition of as little as 0.5 g/mL DEPs to untreated hamster blood significantly shortened closure time in vitro. Conclusions-The intratracheal instillation of DEPs leads to lung inflammation as well as a rapid activation of circulating blood platelets. The kinetics of platelet activation are consistent with the reported clinical occurrence of thrombotic complications after exposure to pollutants. Our findings, therefore, provide a plausible explanation for the increase in cardiovascular morbidity and mortality accompanying urban air pollution.

Coagulation markers in healthy human subjects exposed to diesel exhaust

“…Alternatively, the middle-aged population in epidemiological studies, though free of known cardiovascular disease, may have had some subclinical disease making them relatively more prone to inflammation than our young population. We also did not find a DE-associated increase in platelet numbers, consistent with prior study in a hamster model of DE particle exposure [20]. However, we did not directly test platelet activation, a more sensitive measure for which there is evidence in this hamster model.…”

Particulate matter air pollution exposure promotes recruitment of monocytes into atherosclerotic plaques

“…Studies from several laboratories including our own (15, 19, 32, 48 -50) have demonstrated that a systemic inflammatory response is induced by exposure to ambient particulate matter exposure, supporting the hypothesis put forward by Seaton and colleagues (41). This systemic response is characterized by an increased release of PMN (49) and monocytes (19) from the bone marrow as well as elevated levels of circulating cytokines such as IL-6 and IL-1␤ (48), CRP (36), and procoagulation factors (15,32). Elevated levels of these proinflammatory effector cells and mediators in the circulation have been implicated in the pathogenesis of progression and destabilization Fig.…”

“…Recently several studies have shown that ultrafine particulate matter (UFP) can translocate from the lung into the peripheral blood (32)(33)(34); the biological downstream effects on circulating blood cells and blood vessels are still unclear. We speculate that translocated UFP may contribute to the decrease in circulating monocytes expressing CD11b after PM 10 exposure.…”

Translocation Pathway of the Intratracheally Instilled Ultrafine Particles from the Lung into the Blood Circulation in the Mouse

“…In addition, morphological study showed instilled 30 nm gold particles in capillaries within 30 minutes' postexposure (Berry et al, 1977) and inhaled ultrafine titanium dioxide particles at alveolar wall and in capillaries at 1 hour after the end of exposure (Geiser et al, 2005). UFPs in the blood circulation can directly or indirectly influence hemostasis or cardiovascular integrity and thus induce adverse cardiovascular endpoints more directly (Nemmar et al, 2002b(Nemmar et al, , 2003a(Nemmar et al, , 2003b. The exact pathway for this translocation, however, remains unclear.…”