Particulates Core Highlights -Basic Science
Host defense against inhaled environmental particles and pollutants: Macrophages are known to play a critical role in the clearance of particles and the modulation of inflammatory response. Investigators in our Center have shown that alveolar macrophages express the class A scavenger receptors (SRAs) MARCOand SRA-I/II and that these function as the primary surface receptors for ingestion of pathogens and particles by these cells in mice and humans (Arredouani, Yang et al. 2004; Jozefowski and Kobzik 2004; Arredouani, Palecanda et al. 2005; Arredouani, Yang et al. 2006). Additional studies have identified a novel role for these receptors in clearance of pro-inflammatory oxidized lipids in the airways, as seen after ozone exposure of MARCO-deficient mice (Dahl, Bauer et al. 2007).
Toxic mechanisms of air pollution particles: Lung inflammation is a key response to increased levels of particulate air pollution and oxidants are critical mediators of the inflammatory response elicited by inhalation of ambient air particles (Saldiva, Clarke et al. 2002; Rhoden, Lawrence et al. 2004; Imrich, Ning et al. 2007). Our most recent studies indicate that superoxide anion is a critical mediator of the inflammatory response elicited by ambient particulate in the lung (Rhoden, Ghelfi et al. 2008). Center investigators also developed a murine model of the increased susceptibility to pneumonia caused by particles, and identified oxidant-dependent dysfunction in macrophages and neutrophils as the mechanism for diminished host resistance to pneumococcal pneumonia (Sigaud, Goldsmith et al. 2007).
Physiological mechanisms of cardiorespiratory effects of ambient particles: Center investigators have pioneered controlled laboratory exposures of animals to concentrated ambient particles to produce physiological responses, such as changes in breathing pattern, blood pressure, and blood flow (Godleski et al 2000; Godleski 2006). These studies have expanded to specific measurements of reactive oxygen species in the heart and lungs (Gurgueira, Lawrence et al. 2002; Rhoden, Wellenius et al. 2005). The inter-relationship of these health effects has now been defined by blocking afferent neural response fibers in the lung which mediate autonomic nervous system responses. In these studies, increases in reactive oxygen species in the heart with particle exposures were abrogated by blocking pulmonary neural afferent fibers. Changes in cardiac conduction times observed with the inhalation of ambient particles were also abrogated by blocking the pulmonary afferent fibers (Ghelfi, Rhoden et al. 2008).