Quantification of extrapulmonary translocation of intratracheal-instilled particles in vivo in rats: Effect of lipopolysaccharide

Particulate air pollution is associated with respiratory and cardiovascular morbidity and mortality. However, important uncertainties remain in the quantification of extrapulmonary translocation of ultrafine particles into blood circulation. Therefore, the widely used radioiodinated technique was applied to radiolabel polystyrene particles with an average diameter of 56.4 and 202 nm, respectively. The extrapulmonary distribution of these particles (3.7 × 10⁵ Bq/rat) was quantified at 0.5, 2, 24 and 120 h after intratracheal instillation in rats. Moreover, we have taken into account the possible involvement of pulmonary inflammation in this process. Rats which received a single intratracheal instillation of free ¹²⁵I or a single intravenous injection of labeled ultrafine particles served as control. The results indicated that the pulmonary deposition of radioactivity was almost unchanged for both sizes. Only small amounts of radioactivity (1.64-2.49%) were recovered in blood shortly after administration of both types of particle, in healthy rats. However, the extent of particle translocation into the blood of the ultrafine size following the pretreatment with lipopolysaccharides was significantly higher (from 1.96 ± 0.67 to 4.73 ± 0.31%) compared to larger particles (from 2.19 ± 0.77 to 2.21 ± 0.64%). In conclusion, our findings suggest that only a small fraction of intratracheal-instilled ultrafine particles can pass rapidly into systemic circulation, but this translocation is markedly increased following LPS pretreatment. Thus, pulmonary inflammation seems to play a major role in enhancing the extrapulmonary translocation of particles.