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Updated: Jul 19, 2026

Generation of a Chronic Obstructive Pulmonary Disease Model in Mice by Repeated Ozone Exposure
Published on: August 25, 2017
Inflammatory cell influx into ozone-exposed guinea pig lung interstitial and airways spaces
1Environmental Health Sciences Center, Johns Hopkins University School of Hygiene and Public Health, Baltimore, MD 21205.
Abstract:
As a model of non-immunological lung inflammation, guinea pigs were exposed to 2.0 ppm ozone for 4 hours. Polymorphonuclear leukocytes (PMNs) rapidly accumulated in lung interstitium but declined from 147 +/- 34 million cells to control values (33 +/- 6 million cells) within the first 24 hours. Bronchoalveolar lavage (BAL) recovered PMNs were maximal by 3-6 hours (4 +/- 1 million cells) and remained elevated for 3 days. Macrophage numbers were doubled in lavageable spaces but those in interstitium increased by only a third at 2 days post-exposure. By 7 days post-exposure BAL macrophages had declined to control values of 12 +/- 2 million cells while those in interstitium remained elevated through 14 days. These data demonstrate that BAL does not necessarily reflect cellular changes in lung interstitium.
Insights
Ozone exposure causes lung inflammation in guinea pigs. Bronchoalveolar lavage (BAL) cell counts may not accurately reflect interstitial lung inflammation, highlighting the importance of considering both measures.
Area of Science:
- Pulmonary toxicology
- Respiratory inflammation research
- Cellular immunology
Background:
- Ozone is a known respiratory irritant causing lung inflammation.
- Assessing lung inflammation often involves analyzing cells obtained via bronchoalveolar lavage (BAL).
- The relationship between BAL cellularity and interstitial lung changes requires further investigation.
Purpose of the Study:
- To investigate the temporal dynamics of inflammatory cell accumulation and resolution in the lung interstitium and BAL following ozone exposure.
- To compare cellular changes in the lung interstitium versus those detected in BAL fluid.
- To evaluate the utility of BAL as a sole indicator of ozone-induced lung inflammation.
Main Methods:
- Guinea pigs were exposed to 2.0 ppm ozone for 4 hours.
- Lung tissue and bronchoalveolar lavage (BAL) fluid were collected at various time points post-exposure.
- Polymorphonuclear leukocytes (PMNs) and macrophages were quantified in both interstitial and lavageable spaces.
Main Results:
- PMNs rapidly accumulated in the lung interstitium but returned to baseline within 24 hours, while BAL PMNs remained elevated for 3 days.
- Macrophage numbers doubled in BAL fluid but increased less significantly in the interstitium.
- Interstitial macrophages remained elevated for 14 days, whereas BAL macrophages returned to control levels by 7 days.
Conclusions:
- Bronchoalveolar lavage (BAL) findings may not accurately represent the full extent of cellular changes occurring in the lung interstitium after ozone exposure.
- Ozone-induced lung inflammation involves distinct temporal patterns of cellular infiltration and resolution in different lung compartments.
- Evaluating both interstitial and BAL cellularity provides a more comprehensive understanding of lung inflammation dynamics.
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Chronic Obstructive Pulmonary Disease-II: Pathophysiology
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