Published ahead of print on September 11, 2003, doi:10.1164/rccm.200306-801OC
Am. J. Respir. Crit. Care Med., Volume 168, Number 11, December 2003, 1366-1372
A more recent version of this article appeared on December 1, 2003
Submitted on June 17, 2003
Accepted on September 5, 2003
PULMONARY INFLAMMATION AND THROMBOGENICITY CAUSED BY DIESEL PARTICLES IN HAMSTERS: ROLE OF HISTAMINE
Abderrahim Nemmar1*, Benoit Nemery1, Peter H.M. Hoet1, Jos Vermylen2, and Marc F Hoylaerts2
1 Laboratory of Pneumology (Lung Toxicology), K.U.Leuven, Leuven, Belgium,
2 Center of Molecular and Vascular Biology, K.U.Leuven, Leuven, Belgium
* To whom correspondence should be addressed. E-mail: abderrahim.nemmar{at}med.kuleuven.ac.be.
Short-term increases in particulate air pollution are associated with increased incidence of cardiovascular events. Previously, we showed that intratracheally instilled diesel exhaust particles (DEP) are prothrombotic. Here, we investigated the time course and the mechanisms. One, 6 and 24 h after instillation of 50 µg DEP/hamster, the mean size of in vivo induced and quantified venous thrombosis was increased by 480%, 770% and 460%, respectively. Platelet activation in blood was confirmed by a shortened closure time in the platelet function analyser (PFA-100). In bronchoalveolar lavage (BAL), neutrophils and histamine levels were increased at all time points. In plasma, histamine was increased at 6 and 24 h, but not at 1 and 3 h. Pretreatment with a histamine H1-receptor antagonist (diphenhydramine, 30 mg/kg i.p.) abolished the DEP-induced neutrophil influx in BAL at all time points. However, diphenhydramine pretreatment did not affect DEP-induced thrombosis or platelet activation at 1 h, whereas both were markedly reduced at 6 and 24 h. In conclusion, pulmonary inflammation and peripheral thrombosis are correlated at 6 and 24 h but at 1 h, the prothrombotic effects do not appear to result from pulmonary inflammation but possibly from the blood penetration of DEP-associated components or by DEP-particles themselves.
Key words: Air pollution, particles, Thrombosis, Lung inflammation, Histamine
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