Published Online
on February 24, 2003

A more recent version of this article appeared on March 4, 2003

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Submitted on September 19, 2002
Revised on November 21, 2002
Accepted on November 25, 2002

Diesel Exhaust Particles in Lung Acutely Enhance Experimental Peripheral Thrombosis

Abderrahim Nemmar DVM, PhD, Peter H.M. Hoet PhD, David Dinsdale PhD, Jozef Vermylen MD, PhD, Marc F. Hoylaerts PhD, and Benoit Nemery MD, PhD^*

From the Laboratory of Pneumology, Unit of Lung Toxicology (A.N., P.H.M.H., B.N.), and Center for Molecular and Vascular Biology (J.V., M.F.H.), Kapholieke Universiteit Leuven, Leuven, Belgium, and Medical Research Council Toxicology Unit (D.D.), Leicester, United Kingdom.

^* To whom correspondence should be addressed. E-mail: ben.nemery{at}med.kuleuven.ac.be.

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 µg 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 µg 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 µg/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.

Key words: thrombosis • lung • inflammation • air pollution

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