Traffic-emitted ultrafine particles disrupt macrophage efferocytosis and resolution of allergic lung inflammation.

Abstract

BACKGROUND: Particulate matter (PM) in air pollution is a major health concern. PM includes ultrafine particles (UFPs; PMand particles of ≤0.1 μm), which can evoke lung inflammation. However, the impact of UFPs on the resolution of lung inflammation, a potentially important link to chronic inflammatory diseases, remains to be determined. OBJECTIVE: We sought to investigate the impact of UFPs on the resolution of allergic lung inflammation and to identify potential therapeutic interventions to mitigate these effects. METHODS: UFPs were collected from urban Boston. Using a mouse model, transient allergic lung inflammation was induced by exposure to house dust mite. Mice were then exposed to UFPs, and their inflammatory responses were assessed. The therapeutic potential of a resolution agonist, resolvin D2 (RvD2; 7S,16R,17S-trihydroxy-4Z,8E,10Z,12E,14E,19Z-docosahexaenoic acid), was also determined. RESULTS: UFP exposure impaired lung eosinophil clearance and reduced macrophage efferocytosis, key processes in resolving lung inflammation. This disruption was mediated by altered expression of ecto-5'-nucleotidase (Nt5e, gene encoding for CD73). Administration of RvD2, a potent proresolving mediator, increased macrophage efferocytosis of apoptotic eosinophils and neutrophils and partially corrected the UFP-disrupted resolution mechanisms. CONCLUSIONS: Environmental exposure to traffic-emitted UFPs can fundamentally undermine endogenous resolution processes-pathologic mechanisms that can be partially rescued by signaling pathways activated by RvD2.