Visualizing Cellular Adaptations during Ozone‐induced Lung Inflammation
Bibliographic record
Abstract
Ozone (O 3 ) is a prevalent environmental pollutant with well‐documented acute and chronic health effects. Neutrophils are known as the prime orchestrators of lung immune surveillance. Although bacterial infections are known to elicit a robust lung neutrophil and alveolar macrophage response, it is not known why and how neutrophils are activated in response to sterile lung injury. Acute exposures to 2 ppm O 3 induce lung macrophage and neutrophil extravasation and airway hyper‐reactivity at 24 h, however, these concentrations are manifold higher than ambient O 3 concentrations, thus precluding any understanding of the initial events. Our pilot experiments established ozone's dose and time dependent killing of alveolar macrophages and concomitant recruitment of leukocytes. Our data indicated that 50 ppb of O 3 induces cell death in half of the lung alveolar macrophage population. Thereafter, we exposed C57BL6 mice to either filtered air or 50 ppb of O 3 for 2 h to understand the kinetics of murine ozone induced acute lung injury. We report acute vascular neutrophil concentration and activation at as early as 2 h post exposure which continues up to 24 h after ozone exposure. Immunofluorescent staining revealed CD11b positive lung alveolar macrophage and neutrophil recruitment. In addition to conventional bronchoalveolar lavage, lung vascular perfusate and peripheral blood analysis, we present novel application of simple, yet powerful, configuration of a fixed‐stage wide‐field upright fluorescent intravital microscopic set‐up to investigate ozone's oxidative lung damage. We observed extensive alveolar actin filament disorganization (Fig. 1), an initial drop (at 2 h post‐O 3 exposure) followed by restoration (18 h post‐O 3 exposure) of alveolar reactive oxygen species (ROS) (Fig. 2) as well as mitochondrial potential (Fig. 3) in live animals. Important findings from these preliminary experiments include CD11b predominant phenotypes of pulmonary leukocytes, alveolar necrosis, actin disorganization, acute alterations in alveolar ROS production as well as mitochondrial potential. Thus, we present evidence of systemic as well as lung toxicity at 40 fold lower O 3 concentrations. The findings are important in establishing a sensitive model of ozone induced acute lung injury. Support or Funding Information Fedoruk Centre and Innovation Saskatchewan. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".