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Updated: Aug 23, 2026
Harvesting Murine Alveolar Macrophages and Evaluating Cellular Activation Induced by Polyanhydride Nanoparticles
Published on: June 8, 2012
A comparison of murine and human alveolar macrophage responses to urban particulate matter
Chrysanthus J Obot1, Maria T Morandi, Raymond F Hamilton
1Environmental Toxicology, Texas Southern University, Houston, Texas, USA.
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.
Insights
Fine airborne particulate matter (PM) causes respiratory issues. This study shows that BALB/c mice and human alveolar macrophages (AM) respond similarly to PM exposure, validating mice as a model for human PM toxicity research.
Area of Science:
- Environmental Health
- Toxicology
- Cell Biology
Background:
- Increasing evidence links airborne fine particulate matter (PM) to mortality and respiratory diseases.
- Biological mechanisms underlying PM toxicity in humans remain poorly understood.
- Rodent models are used to study PM toxicity, but their direct relevance to human responses is not fully established.
Purpose of the Study:
- To investigate the mechanisms of PM-induced apoptosis and necrosis in human and murine alveolar macrophages (AM).
- To compare the in vitro cytotoxicity of PM in human and BALB/c mouse AM.
- To evaluate the BALB/c mouse as a predictive model for human AM responses to PM.
Main Methods:
- Human and BALB/c mouse AM were exposed in vitro to different residual fractions of PM1648 with altered surface characteristics.
- Cytotoxicity, apoptosis, and necrosis were assessed following PM exposure.
- In vitro cytotoxicity of PM2.5 particles was compared between human and murine AM.
- Regression analysis was used to compare murine and human AM responses.
Main Results:
- Both human and BALB/c mouse AM exhibited similar patterns of toxicity and post-treatment effects at equivalent PM concentrations.
- Altering PM surface chemistry significantly affected PM bioactivity in both human and murine AM similarly.
- PM2.5 particles demonstrated identical cytotoxic effects in both human and mouse AM models.
- Regression analysis confirmed that BALB/c mice are a suitable model for predicting human AM responses to PM.
Conclusions:
- The BALB/c mouse model effectively mimics human AM responses to PM exposure, including cytotoxicity, apoptosis, and necrosis.
- Modifications to PM surface chemistry similarly impact bioactivity in both human and murine AM.
- The BALB/c mouse serves as a valuable and predictive animal model for understanding human health effects of airborne particulate matter.
