Published Online
on September 13, 2004

A more recent version of this article appeared on September 21, 2004

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Submitted on October 31, 2003
Revised on April 29, 2004
Accepted on May 3, 2004

Pharmacological Stabilization of Mast Cells Abrogates Late Thrombotic Events Induced by Diesel Exhaust Particles in Hamsters

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

From the Laboratory of Pneumology, Lung Toxicology Unit (A.N., P.H.M.H., B.N.), and the Center for Molecular and Vascular Biology (J.V., M.F.H.), Katholieke Universiteit Leuven, Leuven, Belgium.

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

Background--Particulate air pollution is associated with cardiovascular diseases and myocardial infarction (MI).

Methods and Results--We investigated the relationship between airway inflammation and thrombosis 24 hours after intratracheal (IT) instillation of diesel exhaust particles (DEP; 50 µg/hamster). Mild thrombosis was induced in the femoral vein by endothelial injury, and the consequences of airway inflammation on thrombogenicity were studied via online video microscopy. Lung inflammation and histamine analysis in bronchoalveolar lavage (BAL) and plasma were performed after pretreatment with dexamethasone (DEX) or sodium cromoglycate (SC). DEP induced airway inflammation and histamine release in BAL and in plasma, and increased thrombosis, without elevating plasma von Willebrand factor (vWF) levels. The IT instillation of 400-nm positively charged polystyrene particles (500 µg/hamster), serving as particles that do not penetrate into the circulation, equally produced airway inflammation, histamine release, and enhanced thrombosis. Histamine in plasma resulted from basophil activation. Intraperitoneal (IP) pretreatment with DEX (5 mg/kg) abolished the DEP-induced histamine increase in BAL and plasma and abrogated airway inflammation and thrombogenicity. The IT pretreatment with DEX (0.5 mg/kg) showed a partial but parallel inhibition of all of these parameters. Pretreatment with SC (40 mg/kg, IP) strongly inhibited airway inflammation, thrombogenicity, and histamine release.

Conclusions--Our results are compatible with the triggering of mast cell degranulation and histamine release by DEP. Histamine plays an initial central role in airway inflammation, further release of histamine by circulating basophils, and peripheral thrombotic events. Antiinflammatory pretreatment can abrogate the peripheral thrombogenicity by preventing histamine release from mast cells.

Key words: lung • respiration • thrombosis • air pollution

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