Characterization of low‐dose ozone‐induced murine acute lung injury
Bibliographic record
Abstract
Ozone is a toxic and highly reactive gaseous oxidizing chemical with well-documented adverse health effects in humans. On the basis of animal and human data, environmental guidelines and air quality standards recommend a threshold for exposure of no more than 0.063 ppm of ozone (daily concentrations). This research describes a standardized sensitive model of sterile murine lung inflammation induced by exposing mice to acute (0, 4 or 24 hr), yet low, levels of ozone (0.005, 0.05 or 0.5 ppm), one that are below the current recommendations for what is considered a safe or "ambient" ozone concentration for humans. Ozone led to concentration and time-dependent phlogistic cell death in the bronchoalveolar lavage, lung epithelial damage and hemorrhage. Interestingly, we observed distinct large bright CD11b positive cells in the bronchoalveolar lavage, upregulation of lung vascular and alveolar ATP synthase as well as plasminogen and bronchiolar angiostatin expression in ozone-exposed mice, platelet and neutrophil accumulation in the lung vasculature and an eotaxin-2, IL-16, CXCL5, CXCL12, and CXCL13 dominant inflammatory response leading to lung injury. Using a fluorescent intravital microscopy set up, we quantified ozone-induced extensive alveolar cellular damage. We observed ozone-induced actin filament disorganization, perturbed respiratory mechanics, acute suppression of the alveolar reactive oxygen species (ROS) production and mitochondrial potential in ventilated lungs. We present evidence of systemic, as well as pulmonary toxicity, at 40-fold lower ozone concentrations than previously reported in mice. The findings are important in establishing a sensitive means of quantifying structural and functional lung disorganization following exposure to an aerosolized pollutant, even at levels of ozone exposure previously thought to be safe in humans.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".