Possible mechanisms of the cardiovascular effects of inhaled particles: systemic translocation and prothrombotic effects.
Particulate air pollution is associated with cardiovascular morbidity and mortality. Fine particles with a diameter <2.5 microm (PM2.5) have an important role in triggering biological responses. These particles, and particularly the ultrafine fraction (<100 nm) penetrate deeply into the respiratory tract. Recently, we have demonstrated that ultrafine particles are able to translocate from the lung into the systemic circulation in hamsters and humans. In urban areas, diesel engines are considered to be the major source of PM2.5. We therefore evaluated the acute effect (1 h) of diesel exhaust particles (DEP) in a hamster model of peripheral vascular thrombosis induced by free-radical mediated endothelial injury, using intravenous Rose Bengal and local illumination. Intratracheal doses of 5-500 microg of DEP per animal induced inflammation with elevation of neutrophils, total proteins and histamine in bronchoalveolar lavage. DEP enhanced experimental arterial and venous platelet rich-thrombus formation in vivo. Blood samples taken from hamsters 30 and 60 min after instillation of DEP caused platelet activation, when analyzed in the Platelet Function Analyser (PFA-100). The direct addition of DEP to untreated hamster blood also caused platelet aggregation. These effects persisted up to 24 h after instillation. Our results provide plausible mechanistic explanations for the epidemiologically established link between air pollution and acute cardiovascular effects.
Nemmar
Abderrahim
A
Laboratory of Pneumology, Unit of Lung Toxicology, K.U. Leuven, Herestraat, 49, Leuven 3000, Belgium. abderrahim.nemmar@med.kuleuben.ac.be
Hoylaerts
Marc F
MF
Hoet
Peter H M
PH
Nemery
Benoit
B
D000328:Adult; D000393:Air Pollutants / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D006224:Cricetinae; D006801:Humans; D019570:Inhalation Exposure; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects; D010316:Particle Size; D010979:Platelet Function Tests; D011014:Pneumonia / Q000139:chemically induced / Q000473:pathology; D011137:Polystyrenes; D019275:Radiopharmaceuticals; D013670:Sodium Pertechnetate Tc 99m; D013927:Thrombosis / Q000097:blood / Q000139:chemically induced*; D001335:Vehicle Emissions / Q000633:toxicity
D000393:Air Pollutants; D011137:Polystyrenes; D019275:Radiopharmaceuticals; D001335:Vehicle Emissions; C056708:Technegas; D013670:Sodium Pertechnetate Tc 99m