OZONE-INDUCED ALTERATIONS IN MACROPHAGE FUNCTION AND THE PROTECTIVE ROLE OF SR-BI

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Miles Hodge (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Abstract: Ozone (O3), a criteria air pollutant, is the primary component of photochemical smog. Currently, over 140 million people in the United States are exposed to levels of O3 deemed unhealthy by the Environmental Protection Agency. Short and long-term exposure to O3 has been associated with increased susceptibility and/or exacerbations of chronic pulmonary diseases through lung injury and inflammation. O3 induces pulmonary inflammation in part through generating damage associated molecular patterns (DAMPs), which are recognized by pattern recognition receptors (PRRs), such as toll like receptors (TLRs) and scavenger receptors (SRs). This inflammatory response is mediated by alveolar macrophages (AMs) which highly express PRRs, including Scavenger Receptor B-I (SR-BI). SR-BI is a PRR known to recognize DAMPs, apoptotic cells, and facilitate the phagocytosis of apoptotic cells termed -˜efferocytosis". The central hypothesis of this study was that SR-BI resolves O3-induced inflammation and injury by facilitating clearance of DAMPs and maintaining alveolar macrophage efferocytosis. The first aim of this study was to determine whether acute O3 exposure impairs AM efferocytosis whereas the second aim of this study was to determine if SR-BI mediates AM efferocytosis following O3 exposure leading to resolution of lung inflammation and/or injury. Our findings demonstrated that acute O3 exposure impairs AM efferocytosis. Additionally, we proved that SR-BI is protective against O3-induced lung inflammation by decreasing airspace neutrophilia and maintaining AM efferocytosis. Collectively, these results identified novel mechanisms of how O3 induces pulmonary inflammation and increase the susceptibility and/or exacerbations of chronic lung diseases.

Additional Information

Publication

Dissertation

Language: English

Date: 2020

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