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Ozone reduces murine alveolar and peritoneal macrophage phagocytosis: the role of prostanoids
B J Canning1, R R Hmieleski, E W Spannhake
1Department of Environmental Health Sciences, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland 21205.
Abstract:
Continuous ozone exposure (0.5 ppm, 1-14 days) reduced the phagocytic activity of murine alveolar and peritoneal macrophages. The response of peritoneal macrophages to ozone was virtually indistinguishable from the response of alveolar macrophages. When added exogenously, prostaglandin E2 (PGE2) inhibited alveolar and peritoneal macrophage phagocytosis. To test the hypothesis that prostanoids mediated the effects of ozone on macrophages, PGE levels of bronchoalveolar lavage fluid (BALF) and the phagocytic activity of macrophages from ozone-exposed mice pretreated with cyclooxygenase inhibitors were measured. PGE levels in BALF were increased following ozone exposure, with high levels of PGE associated with large decreases in phagocytic activity. Pretreatment with indomethacin and d-naproxen completely inhibited ozone-induced increases in PGE recovered by BAL and the suppression of peritoneal macrophage phagocytic activity. The inactive enantiomer of naproxen, l-naproxen, was without effect. Indomethacin partially inhibited ozone-induced suppression of alveolar macrophage phagocytic activity. These observations suggest that prostanoids play a key role in the response to ozone.
Insights
Ozone exposure impairs macrophage phagocytosis, a key immune function. Prostanoids, like prostaglandin E2 (PGE2), mediate this ozone effect, suggesting therapeutic targets for respiratory inflammation.
Area of Science:
- Immunology
- Environmental Health
- Cell Biology
Background:
- Ozone is a major air pollutant with known respiratory effects.
- Macrophages play a critical role in lung immunity and host defense.
- Ozone exposure is known to affect macrophage function, but the underlying mechanisms are not fully understood.
Purpose of the Study:
- To investigate the role of prostanoids in mediating the effects of ozone exposure on macrophage phagocytic activity.
- To determine if prostaglandin E2 (PGE2) levels are altered by ozone exposure and correlate with changes in macrophage function.
Main Methods:
- Murine alveolar and peritoneal macrophages were exposed to continuous ozone (0.5 ppm) for 1-14 days.
- Phagocytic activity of macrophages was measured.
- Prostaglandin E (PGE) levels in bronchoalveolar lavage fluid (BALF) were quantified.
- Mice were pretreated with cyclooxygenase inhibitors (indomethacin, d-naproxen) before ozone exposure.
Main Results:
- Continuous ozone exposure significantly reduced the phagocytic activity of both alveolar and peritoneal macrophages.
- Ozone exposure led to increased PGE levels in BALF, which correlated with decreased macrophage phagocytosis.
- Pretreatment with indomethacin and d-naproxen blocked ozone-induced increases in PGE and protected against the suppression of peritoneal macrophage phagocytosis.
- The inactive enantiomer l-naproxen had no effect, confirming the specificity of the prostanoid pathway.
Conclusions:
- Prostanoids, particularly PGE2, play a significant role in mediating the inhibitory effects of ozone exposure on macrophage phagocytic activity.
- Inhibition of cyclooxygenase pathways can prevent ozone-induced impairment of macrophage function.
- These findings highlight prostanoids as potential therapeutic targets for mitigating the adverse effects of ozone on lung immunity.