Increased inflammation and altered macrophage chemotactic responses caused by two ultrafine particle types.

BACKGROUND: Ultrafine particles have been hypothesised to be an important contributing factor in the toxicity and adverse health effects of particulate air pollution (PM10) and nanoparticles are used increasingly in industrial processes. AIMS: To compare the ability of ultrafine and fine particles of titanium dioxide and carbon black to induce inflammation, cause epithelial injury, and affect the alveolar macrophage clearance functions of phagocytosis and chemotaxis in vivo. METHODS: Rats were instilled with fine and ultrafine carbon black and titanium dioxide. Inflammation was quantified by bronchoalveolar lavage; the ability of the macrophages to phagoytose indictor fluorescent beads and to migrate towards aC5a were determined. RESULTS: Ultrafine particles induced more PMN recruitment, epithelial damage, and cytotoxicity than their fine counterparts, exposed at equal mass. Both ultrafine and fine particles significantly impaired the phagocytic ability of alveolar macrophages. Only ultrafine particle treatment significantly enhanced the sensitivity of alveolar macrophages to chemotact towards C5a. CONCLUSIONS: Ultrafine particles of two very different materials induced inflammation and epithelial damage to a greater extent than their fine counterparts. In general, the effect of ultrafine carbon black was greater than ultrafine titanium dioxide, suggesting that there are differences in the likely harmfulness of different types of ultrafine particle. Epithelial injury and toxicity were associated with the development of inflammation after exposure to ultrafines. Increased sensitivity to a C5a chemotactic gradient could make the ultrafine exposed macrophages more likely to be retained in the lungs, so allowing dose to accumulate.

Impairment of alveolar macrophage phagocytosis by ultrafine particles.

We investigated whether slowed clearance after exposure to ultrafine particles was due to a failure in alveolar macrophage phagocytosis. This was achieved by measuring the ability of a macrophage cell line (J774.2 MPhi) to phagocytose 2-microg indicator latex beads following 8-h exposures to a number of test particles. Particles utilized were fine titanium dioxide (TiO2), ultrafine titanium dioxide (UTiO2), carbon black (CB), or ultrafine carbon black (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 macrophages. Ultrafine and fine particles had no significant cytotoxic effects on J774.2 MPhi. A significant reduction in the ability of macrophages to phagocytose the indicator beads occurred after exposure to 0.39 microg/mm(2) (p < 0.001) of UCB and 0.78 microg/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 microg/mm(2), respectively). At all doses, UCB resulted 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 macrophages had no significant effect on the phagocytic ability of macrophages, suggesting that cell-cell contact is responsible for the pattern of failed phagocytosis (data not shown). We have demonstrated that ultrafine particles impair macrophage phagocytosis to a greater extent than fine particles compared on a mass basis. Therefore, we conclude that slowed clearance of particles, specifically the ultrafines, can in part be attributed to a particle-mediated impairment of macrophage phagocytosis.