Related Experiment Videos
Modification of macrophage adhesion by ozone: role of cytokines and cell adhesion molecules
D K Bhalla1, L A Hoffman, A C Pearson
1Wayne State University, Detroit, Michigan 48202, USA.
Abstract:
The inflammatory response in the lungs following an inhalation exposure of animals and humans to ozone (O3) is associated with macrophage stimulation, release of chemotactic agents, and neutrophilia. This study investigated the adhesive behavior of the alveolar macrophages and its relevance to the inflammatory processes in the lung. Macrophages recovered by BAL from rats exposed to purified air or 0.8 ppm O3 were studied in vitro for their adhesion to epithelial cells derived from ARL-14. The macrophages from O3-exposed animals displayed greater adhesion to the epithelial cells than the macrophages from control rats exposed to purified air. The O3-induced adhesion was attenuated in the macrophages treated with a combination of interleukin-1 alpha and tumor necrosis factor-alpha antibodies (anti-IL-1+anti-TNF). The cell adhesion stimulated by O3 exposure was also attenuated when the macrophages were incubated in the presence of antibodies to leukocyte adhesion molecules, CD11b, or epithelial cell adhesion molecules, ICAM-1. A marginal increase in the surface expression of CD11b was noticed in macrophages from the rats exposed to O3. A similar change in the ICAM-1 expression was, however, not observed. The results suggest that the O3-induced modifications of macrophages are mediated by IL-1 and TNF, and that these modifications are accompanied by a minimal change in the expression of the cell-adhesion molecules.
Insights
Ozone exposure increases lung inflammation by enhancing macrophage adhesion to epithelial cells. This effect is mediated by interleukin-1 and tumor necrosis factor, with minimal changes in cell adhesion molecule expression.
Area of Science:
- Pulmonary immunology
- Environmental toxicology
- Cellular biology
Background:
- Ozone (O3) inhalation triggers lung inflammation, characterized by macrophage activation and neutrophilia.
- Alveolar macrophage behavior is crucial in the lung's inflammatory response to inhaled pollutants.
Purpose of the Study:
- To investigate the adhesive properties of alveolar macrophages post-ozone exposure.
- To determine the role of specific inflammatory mediators and cell adhesion molecules in ozone-induced lung inflammation.
Main Methods:
- Bronchoalveolar lavage (BAL) was used to collect macrophages from rats exposed to ozone or purified air.
- In vitro adhesion assays were performed using macrophages and ARL-14 epithelial cells.
- Macrophages were treated with antibodies against interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), CD11b, and intercellular adhesion molecule-1 (ICAM-1).
Main Results:
- Ozone-exposed rat macrophages exhibited significantly greater adhesion to epithelial cells compared to controls.
- Ozone-induced macrophage adhesion was reduced by antibodies targeting IL-1 and TNF-alpha.
- Adhesion was also attenuated by antibodies against CD11b and ICAM-1, with a slight increase in CD11b surface expression on ozone-exposed macrophages.
Conclusions:
- Ozone exposure alters macrophage behavior, increasing their adhesion to lung epithelial cells.
- Interleukin-1 and tumor necrosis factor play a key role in mediating ozone-induced macrophage adhesion.
- While CD11b expression showed a minor increase, ICAM-1 expression was not significantly altered, suggesting complex regulation of cell adhesion in ozone-induced inflammation.