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Impacts of Inhaled Environmental Particles on Macrophage Inflammatory Functions

Christopher Migliaccio, PhD, PharmD., Research Associate Professor
SURP Student: 
Hailey Madison, SOT Intern, The University of Montana – Western

Exposure to environmental particles can cause long term health effects including obstructive pulmonary disease. A key cell in the response to inhaled environmental exposures is the alveolar macrophage (AM). The AM plays important roles in both the induction and resolution of inflammatory responses. Efferocytosis is the process in which apoptotic cells are recognized and cleared by phagocytic cells that results in reduction of inflammation, which reduces the production of inflammatory cytokines like TNF. The objective of this study is to assess the effects of environmental particles on macrophage functions and the inflammatory process. This study utilized ex vivo and in vitro methods to collect AM and bone marrow-derived macrophages (BMdM). Using an efferocytosis assay, macrophages were cultured with apoptotic bait cells and assessed by flow cytometry. AM were collected from wood smoke (WS) and filtered air (FA) exposed mice, while BMdM were exposed in vitro to five modified crystalline silica particles. Additionally, freshly isolated AM were utilized for ex vivo cultures with LPS-stimulation and cytospin analyses. An ELISA was performed to measure LPS-induced inflammatory cytokines from the ex vivo cultures. The results of the WS-exposed AM versus FA-exposed AM assay showed that WS exposed mice had a lower percent of cells that had performed efferocytosis after 24 hours and even lower two months post WS exposure. Cytospin results revealed no neutrophil influx, while the ELISA assay showed an increase of TNF from AM 24 hours post WS exposure. These results indicate that following inhaled WS exposures, there appears to be an increase in inflammatory potential with respect to AM functions. In addition, exposure of BMdM to modified crystalline silica particles resulted in a dose-dependent decrease in efferocytosis. The present work illustrates a particle effect on the potential for macrophage control of inflammation, as well as a specific and extended effect from inhaled wood smoke.