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Modulation of human alveolar macrophage properties by ozone exposure in vitro
S Becker1, M C Madden, S L Newman
1ABB Environmental Services, Inc., Chapel Hill, North Carolina 27514.
Abstract:
We have investigated changes in human alveolar macrophage (HAM) function after exposure in vitro to ozone (O3) (0.1-1.0 ppm for 2-4 hr). The functions studied reflect concern that O3 is detrimental to host defense mechanisms in the bronchoalveolar spaces. Exposure of HAM to O3 caused a concentration-dependent increase in release of prostaglandin E2 (PGE2), an important modulator of inflammation, phagocytosis, and oxidative burst. Although phagocytosis of particulate immune complexes was decreased by O3, we found no change in the quantity of Fc receptors and complement receptors on the HAM surface. Superoxide (O2-) production in response to phorbol ester was reduced after exposure of HAM to O3 while the basal O2- release in response to plastic adherence was not affected. Growth inhibition of the opportunistic yeast Cryptococcus neoformans by HAM was not affected by O3 exposure. The production of inflammatory mediators and immune modulators such as tumor necrosis factor-alpha, interleukin 1, and interleukin 6 were not induced by exposure to O3. However, compared to controls, O3- exposed HAM produced significantly lower levels of these cytokines when stimulated with bacterial lipopolysaccharide (LPS). Two-dimensional gel electrophoretic analysis of proteins made by HAM following in vitro exposure to O3 identified 11 proteins whose rate of synthesis was significantly altered. Thus, these studies show that exposure to O3 alters the functional competence of HAM. While there is a minimal effect on protein expression or synthesis, the responses of HAM to particulate immune complexes, to bacterial LPS, and to PMA are impaired. The release of arachidonic acid and PGE2 suggest that the effect of O3 is primarily targeted to the HAM cell membrane. These changes may ultimately result in increased susceptibility to inhaled infectious agents in the O3-exposed individual.
Insights
Ozone exposure impairs human alveolar macrophage function, reducing their ability to combat infections. This study highlights how ozone affects immune responses in the lungs, potentially increasing susceptibility to respiratory pathogens.
Area of Science:
- Environmental Health
- Immunology
- Cell Biology
Background:
- Ozone (O3) is a major air pollutant with known respiratory effects.
- Human alveolar macrophages (HAMs) are critical for lung defense against inhaled pathogens.
- Concerns exist regarding O3's detrimental impact on host defense mechanisms in the airways.
Purpose of the Study:
- To investigate the functional changes in HAMs following in vitro exposure to varying concentrations of ozone.
- To assess the effects of O3 on key HAM functions, including inflammatory mediator release, phagocytosis, and oxidative burst.
- To understand the implications of O3-induced HAM dysfunction on host defense.
Main Methods:
- In vitro exposure of HAMs to ozone (0.1-1.0 ppm for 2-4 hours).
- Measurement of prostaglandin E2 (PGE2) release, phagocytosis of immune complexes, and superoxide (O2-) production.
- Assessment of Fc and complement receptor expression.
- Analysis of cytokine production (TNF-α, IL-1, IL-6) after lipopolysaccharide (LPS) stimulation.
- Two-dimensional gel electrophoresis to analyze protein synthesis changes.
Main Results:
- Ozone exposure increased PGE2 release in a concentration-dependent manner.
- Phagocytosis of immune complexes and phorbol ester-stimulated superoxide production were reduced by O3.
- O3-exposed HAMs produced lower levels of cytokines (TNF-α, IL-1, IL-6) when stimulated with LPS.
- No significant changes were observed in Fc/complement receptor quantity or yeast growth inhibition.
- Eleven proteins showed altered synthesis rates following O3 exposure.
Conclusions:
- In vitro ozone exposure alters HAM functional competence, impairing responses to immune complexes, LPS, and phorbol myristate acetate (PMA).
- The primary effect of O3 appears to target the HAM cell membrane, evidenced by altered arachidonic acid and PGE2 release.
- Ozone-induced immune dysfunction in HAMs may lead to increased susceptibility to respiratory infections.