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Release of oxygen products from lung macrophages by N-formyl peptides
Abstract:
Incubation of guinea pig pulmonary macrophages with N-formylmethionylphenylalanine (FMP) resulted in 1) a rapid increase in O2 consumption and 2) an accumulation of superoxide anion and hydrogen peroxide in the extracellular medium. The accumulation of superoxide anion and hydrogen peroxide was completely prevented in the presence of superoxide dismutase and catalase, respectively. FMP-stimulated O2 consumption and superoxide anion and hydrogen peroxide accumulation were proportional to the macrophage concentration, showed similar dependence on FMP concentration, had nearly identical kinetics, and were partially abolished by antimycin A, an inhibitor of mitochondrial respiration. FMP also stimulated a three- to fourfold increase in hexose monophosphate shunt (HMS) activity. Catalase had no effect on the amount of glucose oxidized by the HMS, indicating that removal of hydrogen peroxide was without effect on the observed HMS activity. Since FMP is similar in structure to the oligopeptides of bacterial metabolism, its ability to stimulate the release of these microbiocidal products of oxygen metabolism may be important in vivo.
Insights
N-formylmethionylphenylalanine (FMP) stimulates guinea pig macrophages to consume oxygen and release superoxide anion and hydrogen peroxide. These microbiocidal products of oxygen metabolism may play a role in vivo.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Pulmonary macrophages are key immune cells in the lung.
- Oxygen metabolism in macrophages generates reactive oxygen species (ROS).
- Bacterial peptides can activate immune cells.
Purpose of the Study:
- To investigate the effect of N-formylmethionylphenylalanine (FMP) on guinea pig pulmonary macrophages.
- To determine if FMP stimulates oxygen consumption and ROS production.
- To explore the role of mitochondrial respiration and the hexose monophosphate shunt (HMS) in FMP-mediated responses.
Main Methods:
- Incubation of guinea pig pulmonary macrophages with FMP.
- Measurement of oxygen consumption.
- Quantification of superoxide anion and hydrogen peroxide.
- Enzyme inhibition studies (superoxide dismutase, catalase, antimycin A).
- Assessment of hexose monophosphate shunt (HMS) activity.
Main Results:
- FMP rapidly increased macrophage oxygen consumption.
- FMP induced extracellular accumulation of superoxide anion and hydrogen peroxide.
- These effects were dose-dependent, time-dependent, and partially inhibited by antimycin A.
- FMP significantly increased HMS activity.
- Catalase did not affect HMS activity, suggesting hydrogen peroxide removal is independent of HMS glucose oxidation.
Conclusions:
- FMP stimulates microbiocidal products of oxygen metabolism in pulmonary macrophages.
- Mitochondrial respiration plays a role in FMP-induced responses.
- The hexose monophosphate shunt is activated by FMP.
- FMP's structural similarity to bacterial peptides suggests a potential in vivo role in host defense.