Surface components of airborne particulate matter induce macrophage apoptosis through scavenger receptors

Epidemiology studies have linked mortality, increased asthma morbidity, and other respiratory disorders in urban areas to increases in fine airborne particulate matter (PM) concentrations. However, neither the bioactive components of PM nor the biological mechanisms of the reported health effects have been elucidated. A number of studies have implicated soluble metals, the strong acid fraction, and/or other components of PM as possible bioactive mediators. Alveolar macrophage (AM) apoptosis, mediated through scavenger receptors (SR), may be important in the response to inflammatory particles. Therefore, this study explores the hypothesis that organic and metallic components of PM induce apoptosis by interacting with SR. Freshly isolated AM from Balb/c mice were incubated with PM 1648 samples untreated or extracted with Milli-Q water, acetone, or cyclohexane, acid digested, or heated at 100 or 500 degrees C. Cell viability was assessed by trypan blue exclusion and apoptosis was demonstrated by examination of cell morphology and cell death ELISA. Untreated PM induced necrosis and apoptosis in AM. Treatment of PM by organic extraction, acid digestion, or high heat modified the particle surface composition and apoptosis was decreased. Apoptosis induced by untreated, acetone extracted, and high heat-treated PM was blocked by polyinosinic acid or 2F8 antibody. These results demonstrate that PM-induced apoptosis is mediated by Class A Type I/II SR. Altering the surface characteristics of PM interferes with recognition by SR, resulting in decreased apoptosis of AM. Therefore, altering the surface chemistry by removal of one or more PM components, such as the various treatments conducted in this study, is sufficient to alter PM bioactivity. These results may also help explain why PM from many different sources, with differences in composition, are all bioactive, since it is the overall matrix that is important, not just one component.