ABSTRACT
There is increasing evidence linking mortality, increased asthma morbidity, and other respiratory disorders to increases in fine airborne particulate matter (PM) concentrations. However, there are only limited data dealing with the biological mechanisms that ultimately lead to the reported health effects. Rodents are frequently used as an animal model to help elucidate the mechanisms of toxicity that may provide clues for the understanding of PM toxicity in humans; however, the relationships between murine and human PM toxicity have not been established. PM is known to target the pulmonary epithelium and resident alveolar macrophages (AM). PM can initiate cytotoxic effects on the AM including apoptosis and necrosis, depending on the particle concentration, which may be central to the pathological effects just described. This study examined AM apoptosis and necrosis initiated by PM in AM from humans and BALB/c mice in an in vitro exposure model. Freshly isolated AM from human volunteers were incubated with seven different residual fractions of PM1648 derived from organic solvent extractions, high-temperature heating and acid digestions that change the surface characteristics of the original PM. These results were compared to the analogous murine experiments. The results suggested that, at the same concentration of PM, the trend of toxicity and the posttreatment effects observed in BALB/c and human AM have a similar pattern. Altering the surface chemistry by removal of one or more PM components, such as through the various treatments conducted in this study, is sufficient to alter PM bioactivity in both human and murine AM in a similar manner. In addition, the human and murine models were compared with regard to in vitro cytotoxicity using PM(2.5) particles. The cytotoxic PM(2.5) effects were identical in both human and mouse models. Regression analysis revealed that the BALB/c mouse is a suitable model for PM cytotoxicity of AM as it is a good predictive model for the human AM responses.
Subject(s)
Air Pollutants/toxicity , Macrophages, Alveolar/drug effects , Urban Health , Air Pollutants/chemistry , Animals , Apoptosis/drug effects , Cell Survival/drug effects , Cells, Cultured , Chemical Fractionation , Dose-Response Relationship, Drug , Humans , Macrophages, Alveolar/metabolism , Macrophages, Alveolar/pathology , Mice , Mice, Inbred BALB C , Necrosis , Particle Size , Species Specificity , Surface PropertiesABSTRACT
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.
