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Effect of CO2 on LPS-induced cytokine responses in rat alveolar macrophages
Carol J Lang1, Ping Dong, Emma K Hosszu
1Department of Human Physiology, School of Medicine, Flinders University of South Australia, Adelaide, Australia. carol.lang@adelaide.edu.au
Abstract:
Alveolar macrophages (AM) may be exposed to a range of CO(2) and pH levels depending on their location in the alveoli and the health of the lung. Cytokines produced by AM contribute to inflammation in acute lung injury (ALI). Current ventilatory practices for the management of ALI favor low tidal volumes, which can give rise to increases in CO(2) and changes in pH of the alveolar microenvironment. Here we examined the effect of CO(2) on cytokine release from LPS-stimulated rat AM. AM were incubated for 1-4 h under different atmospheric gas mixtures ranging from 2.5-20% CO(2). To distinguish between effects of pH and CO(2), the culture media were also buffered to pH 7.2 with NaHCO(3). Cell metabolic activity, but not cell viability, decreased and increased significantly after 4 h at 20 and 2.5% CO(2), respectively. Increasing CO(2) decreased TNF-alpha secretion but had no effect on lysate TNF-alpha. Buffering the media abated the effects of CO(2) on TNF-alpha secretion. CO(2) increased cytokine-induced neutrophil chemoattractant factor-1 secretion only when the pH was buffered to 7.2. Effects of CO(2) on cytokine responses were reversible. In conclusion, the effects of CO(2) on cytokine lysate levels and/or secretion in AM are cytokine specific and, depending on both the cytokine and the immediate microenvironment, may be beneficial or detrimental to ALI.
Insights
Elevated carbon dioxide (CO2) levels impact alveolar macrophage (AM) cytokine release, potentially influencing acute lung injury (ALI). The effects of CO2 on cytokine secretion are specific and depend on the microenvironment.
Area of Science:
- Pulmonary Medicine
- Immunology
- Cell Biology
Background:
- Alveolar macrophages (AM) produce cytokines that contribute to lung inflammation in acute lung injury (ALI).
- Mechanical ventilation for ALI often involves low tidal volumes, potentially altering alveolar CO2 and pH.
- The microenvironment's CO2 and pH levels can vary based on lung health and macrophage location.
Purpose of the Study:
- To investigate the impact of varying CO2 concentrations on cytokine release from lipopolysaccharide (LPS)-stimulated rat AM.
- To differentiate the effects of CO2 from pH changes on AM cytokine secretion.
Main Methods:
- Rat AM were cultured under diverse atmospheric CO2 concentrations (2.5-20%) for 1-4 hours.
- Culture media were buffered to pH 7.2 to isolate CO2 effects from pH alterations.
- Cell metabolic activity, viability, and secretion of TNF-alpha and cytokine-induced neutrophil chemoattractant factor-1 (KC) were measured.
Main Results:
- High CO2 (20%) decreased metabolic activity, while low CO2 (2.5%) increased it; cell viability was unaffected.
- Increased CO2 reduced TNF-alpha secretion, an effect mitigated by media buffering.
- CO2 enhanced KC secretion specifically when the media pH was buffered to 7.2.
- Observed effects on cytokine secretion were reversible.
Conclusions:
- CO2 exerts cytokine-specific effects on AM, influencing secretion and potentially lysate levels.
- These CO2-mediated effects can be beneficial or detrimental in ALI, contingent on the specific cytokine and microenvironment.
- Understanding CO2's role is crucial for managing ALI and optimizing ventilatory strategies.
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