Impairment of alveolar macrophage phagocytosis by ultrafine particles

We investigated whether slowed clearance after exposure to ultrafine partic les was due to a failure in alveolar macrophage phagocytosis. This was achi eved by measuring the ability of a macrophage cell line (J774.2 M Phi) to p hagocytose 2-mum indicator latex beads following g-h exposures to a number of test particles. Particles utilized were fine titanium dioxide (TiO2), ul trafine titanium dioxide (UTiO2), carbon black (CB), or ultrafine carbon bl ack (UCB), Cytotoxicity of particles was measured by means of MTT activity. In a preliminary study, we assessed the effects of conditioned medium from particle-treated macrophages on the phagocytic ability of naive macrophage s. Ultrafine and fine particles had no significant cytotoxic effects on J77 4.2 M Phi. A significant reduction in the ability of macrophages to phagocy tose the indicator beads occurred after exposure to 0.39 mug/mm(2) (p < 0.0 01) of UCB and 0.78 mug/mm(2) (p < 0.001) of all particle types compared to the control. Furthermore, ultrafine particles were shown to significantly (p < 0.001) impair macrophage phagocytosis at a lower dose than their fine counterparts (0.39 and 0.78 mug/mm(2), respectively). At all doses, UCB res ulted in a greater number (p < 0.001) of nonphagocytic macrophages compared to the other test particles. We tested whether a diffusable mediator being released from particle-exposed cells inhibited the phagocytic activity of adjacent macrophages, The conditioned medium from particle-exposed macropha ges had no significant effect on the phagocytic ability of macrophages, sug gesting that cell-cell contact is responsible for the pattern of failed pha gocytosis (data not shown). We have demonstrated that ultrafine particles i mpair macrophage phagocytosis to a greater extent than fine particles compa red on a mass basis. Therefore, we conclude that: slowed clearance of parti cles, specifically the ultrafines, can in part be attributed to a particle- mediated impairment of macrophage phagocytosis. (C) 2001 Academic Press.