Background-Pollution by particulates has been consistently associated with increased cardiovascular morbidity and mortality. However, the mechanisms responsible for these effects are not well-elucidated. Methods and Results-To assess to what extent and how rapidly inhaled pollutant particles pass into the systemic circulation, we measured, in 5 healthy volunteers, the distribution of radioactivity after the inhalation of "Technegas," an aerosol consisting mainly of ultrafine 99m Technetium-labeled carbon particles (Ͻ100 nm). Radioactivity was detected in blood already at 1 minute, reached a maximum between 10 and 20 minutes, and remained at this level up to 60 minutes. Thin layer chromatography of blood showed that in addition to a species corresponding to oxidized 99m Tc, ie, pertechnetate, there was also a species corresponding to particle-bound 99m Tc. Gamma camera images showed substantial radioactivity over the liver and other areas of the body. Conclusions-We conclude that inhaled 99m Tc-labeled ultrafine carbon particles pass rapidly into the systemic circulation, and this process could account for the well-established, but poorly understood, extrapulmonary effects of air pollution.

Page 704, credit for the schematic panels in the model of vessel remodeling during lung maturation (Fig. 2c-e) was omitted. The panels were originally published in Fig. 3 of Burri, P.H. Fetal and postnatal development of the lung. Annu. Rev. Physiol. 46, 617-628 (1984). This reference should be added as reference 44 on p. 710. Elsewhere on the same page, the authors erroneously used the term 'alveoli', which refers to structures that form only after birth, to denote 'saccules', which form during the saccular stage of embryonic development. In the legend of Fig. 2, the description of parts c-e should read: "c-e, Schematic illustration of capillary remodeling in septa. During lung development, capillaries around the airspaces establish a close contact with the overlying cuboidal epithelium (c). Perinatally, secondary septa develop from primary septa, containing a double capillary network (d). In the mature lung, interalveolar septa contain a single capillary layer (e)." In the body of the article, the second through fourth full sentences of the right-hand column should be replaced by the following: "In addition, capillaries in the septa failed to remodel properly in HIF-2α-/-mice. During normal lung development 44 , capillaries, which previously formed a loose network within the mesenchyme, arrange themselves around the airspaces, subsequently establishing in many places a close contact with the overlying cuboidal epithelium (Fig. 2c). During the saccular stage, the capillary networks form a capillary bilayer in the intersacullar septa as the airspaces approach each other (Fig. 2d). In the mature lung, interalveolar septa contain a single capillary layer (Fig. 2e)."

The mechanisms of particulate pollution-related cardiovascular morbidity and mortality are not well understood. We studied the passage of radioactively labeled ultrafine particles after their intratracheal instillation. Hamsters received a single intratracheal instillation of 100 microg albumin nanocolloid particles (nominal diameter < or = 80 nm) labeled with 100 microCi technetium-99m and were killed after 5, 15, 30, and 60 min. In blood, radioactivity, expressed as percentage of total body radioactivity per gram blood, amounted to 2.88 +/- 0.80%, 1.30 +/- 0.17%, 1.52 +/- 0.46%, and 0.21 +/- 0.06% at 5, 15, 30, and 60 min, respectively. Thin-layer chromatography showed only one peak of radioactivity corresponding to unaltered (99m)Tc-albumin nanocolloid. In the liver, radioactivity, expressed as percentage of total radioactivity per organ, amounted to 0.10 +/- 0.07%, 0.23 +/- 0.06%, 1.24 +/- 0.27%, and 0.06 +/- 0.02% at 5, 15, 30, and 60 min, respectively. Lower values were observed in the heart, spleen, kidneys, and brain. Dose dependence was assessed at 30 min following instillation of 10 microg and 1 microg (99m)Tc-albumin per animal (n = 3 at each dose), and values of the same relative magnitudes as after instillation of 100 microg were obtained. We conclude that a significant fraction of (99m)Tc-albumin, taken as a model of ultrafine particles, rapidly diffuses from the lungs into the systemic circulation.

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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.