Size effect of intratracheally instilled particles on pulmonary inflammation and vascular thrombosis

Particulate air pollution is associated with cardiorespiratory effects and ultrafine particles (UFPs, diameter < 100 nm) are believed to play an important role. We studied the acute (1 h) effect of intratracheally instilled unmodified (60 nm), negatively charged carboxylate-modified (60 nm), or positively charged amine-modified (60 or 400 nm) polystyrene particles on bronchoalveolar lavage (BAL) indices and on peripheral thrombosis in hamster. The latter was assessed by measuring the extent of photochemically induced thrombosis in a femoral vein via transillumination. Unmodified and negative UFPs did not modify thrombosis and BAL indices. Positive UFPs increased thrombosis at 500 microg per animal (+ 341 +/- 96%) and at 50 microg per animal (+ 533 +/- 122%), but not at 5 microg per animal. Neutrophils, lactate dehydrogenase, and histamine were increased in BAL at all these doses but protein concentration was increased only at 500 microg per animal. Positive 400-nm particles (500 microg per animal) did not affect thrombosis, although they led to a neutrophil influx and an increase in BAL proteins and histamine. Using the Platelet Function Analyser (PFA-100), the platelets of hamsters were activated by the in vitro addition of positive UFPs and 400-nm particles to blood. We conclude that intratracheally administered positive ultrafine and 400-nm particles induce pulmonary inflammation within 1 h. Positive UFPs, but not the 400-nm particles enhance thrombosis. Hence, particle-induced lung inflammation and thrombogenesis can be partially uncoupled.