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Biological dose response to PM2.5: effect of particle extraction method on platelet and lung responses
Laura S Van Winkle1, Keith Bein2, Donald Anderson3
1*Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, Center for Health and the Environment, Air Quality Research Center, Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine and Departments of Mechanical and Aerospace Engineering, Civil and Environmental Engineering, and Land, Air and Water Resources, University of California, Davis, California 95616-8732 *Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, Center for Health and the Environment, Air Quality Research Center, Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine and Departments of Mechanical and Aerospace Engineering, Civil and Environmental Engineering, and Land, Air and Water Resources, University of California, Davis, California 95616-8732 lsvanwinkle@ucdavis.edu.
Abstract:
Particulate matter (PM) exposure contributes to respiratory diseases and cardiopulmonary mortality. PM toxicity is related to sources and composition, such as abundance of polycyclic aromatic hydrocarbons (PAHs). We exposed adult male BALB/c mice, via oropharyngeal aspiration, to a range of doses of PM2.5 collected during the winter in downtown Sacramento near a major freeway interchange (SacPM). Two preparation methods (spin-down and multi-solvent extraction) were tested to remove particles from collection filters. Three doses were analyzed 24 h after treatment for (1) leukocytes and total protein in bronchoalveolar lavage fluid (BALF), (2) airway-specific and whole lobe expression of PAH-sensitive genes (CYP1B1 and CYP1A1) and IL-1 b, (3) lung histology, and (4) platelet function. Both extraction methods stimulated biological responses, but the spin-down method was more robust at producing IL-1 b and CYP1B1 gene responses and the multi-solvent extraction induced whole lung CYP1A1. Neutrophils in the BALF were increased 5- to 10-fold at the mid and high dose for both preparations. Histopathology scores indicated dose-dependent responses and increased pathology associated with spin-down-derived PM exposure. In microdissected airways, spin-down PM increased CYP1B1 gene expression significantly, but multi-solvent extracted PM did not. Platelet responses to the physiological agonist thrombin were approximately twice as potent in the spin-down preparation as in the multi-solvent extract. We conclude (1) the method of filter extraction can influence the degree of biological response, (2) for SacPM the minimal effective dose is 27.5-50 µg based on neutrophil recruitment, and (3) P450s are upregulated differently in airways and lung parenchyma in response to PAH-containing PM.
Insights
Exposure to Sacramento PM2.5 air pollution, particularly from the spin-down preparation method, increased inflammation and altered gene expression in mice lungs. The extraction method significantly impacts observed biological responses and toxicity.
Area of Science:
- Environmental Health
- Toxicology
- Pulmonary Medicine
Background:
- Particulate matter (PM) exposure is linked to respiratory diseases and mortality.
- Polycyclic aromatic hydrocarbons (PAHs) in PM contribute to its toxicity.
- Understanding PM2.5 effects requires standardized preparation methods.
Purpose of the Study:
- To evaluate the biological effects of Sacramento PM2.5 (SacPM) on mouse lungs.
- To compare the impact of two different PM preparation methods (spin-down vs. multi-solvent extraction).
- To determine dose-dependent responses and identify minimal effective doses.
Main Methods:
- Adult male BALB/c mice were exposed to varying doses of SacPM via oropharyngeal aspiration.
- Two extraction methods were used to process collected PM2.5 filters.
- Assessed outcomes included bronchoalveolar lavage fluid (BALF) analysis, gene expression (CYP1B1, CYP1A1, IL-1β), lung histology, and platelet function.
Main Results:
- Both preparation methods induced biological responses, with spin-down showing stronger IL-1β and CYP1B1 responses.
- Neutrophil counts in BALF increased significantly (5-10 fold) at mid and high doses.
- Spin-down PM exposure led to increased lung pathology and potent platelet activation compared to multi-solvent extraction.
Conclusions:
- The method used to extract PM from filters significantly influences the observed biological responses and toxicity.
- The minimal effective dose of SacPM for neutrophil recruitment was determined to be 27.5-50 µg.
- PAH-containing PM differentially upregulates P450 enzymes in lung airways versus parenchyma.
