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

Abstract

Particulate matter (PM) in air pollution is a major health concern. PM includes ultrafine particles (UFPs; PM_0.1 and 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. 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. 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. 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. 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.