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Propofol suppresses macrophage functions and modulates mitochondrial membrane potential and cellular adenosine
Ruei-Ming Chen1, Chih-Hsiung Wu, Huai-Chia Chang
1Department of Anesthesiology, Wan-Fang Hospital, College of Medicine, Taipei Medical University, No. 111, Sec. 3, Hsing-Lung Road, Taipei 116, Taiwan. chen01@wanfang.gov.tw
Background:
Propofol is an intravenous anesthetic agent that may impair host defense system. The aim of this study was to evaluate the effects of propofol on macrophage functions and its possible mechanism.
Methods:
Mouse macrophage-like Raw 264.7 cells were exposed to propofol, at 3, 30 (a clinically relevant concentration), and 300 microm. Cell viability, lactate dehydrogenase, and cell cycle were analyzed to determine the cellular toxicity of propofol to macrophages. After administration of propofol, chemotactic, phagocytic, and oxidative ability and interferon-gamma mRNA production were carried out to validate the potential effects of propofol on macrophage functions. Mitochondrial membrane potential and cellular adenosine triphosphate levels were also analyzed to evaluate the role of mitochondria in propofol-induced macrophage dysfunction.
Results:
Exposure of macrophages to 3 and 30 microm propofol did not affect cell viability. When the administered concentration reached 300 microm, propofol would increase lactate dehydrogenase release, cause arrest of cell cycle in G1/S phase, and lead to cell death. In the 1-h-treated macrophages, propofol significantly reduced macrophage functions of chemotactic and oxidative ability in a concentration-dependent manner. However, the suppressive effects were partially or completely reversed after 6 and 24 h. Propofol could reduce phagocytic activities of macrophages in concentration- and time-dependent manners. Exposure of macrophages to lipopolysaccharide induced the mRNA of interferon-gamma, but the induction was significantly blocked by propofol. Propofol concentration-dependently decreased the membrane potential of macrophage mitochondria, but the effects were descended with time. The levels of cellular adenosine triphosphate in macrophages were also reduced by propofol.
Conclusions:
A clinically relevant concentration of propofol can suppress macrophage functions, possibly through inhibiting their mitochondrial membrane potential and adenosine triphosphate synthesis instead of direct cellular toxicity.
Insights
Propofol, a common anesthetic, impairs macrophage function at clinically relevant doses by reducing mitochondrial activity and ATP synthesis, not direct cell damage. This affects host defense mechanisms.
Area of Science:
- Immunology
- Pharmacology
- Cell Biology
Background:
- Propofol is an intravenous anesthetic.
- Anesthetics like propofol can potentially impair the host defense system.
- The effects of propofol on macrophage function require detailed investigation.
Purpose of the Study:
- To evaluate the impact of propofol on macrophage functions.
- To elucidate the underlying mechanisms of propofol's effects on macrophages.
- To assess propofol's cellular toxicity and its influence on immune cell activity.
Main Methods:
- Mouse macrophage-like Raw 264.7 cells were treated with varying concentrations of propofol.
- Cell viability, lactate dehydrogenase release, and cell cycle were analyzed.
- Macrophage functions including chemotaxis, phagocytosis, oxidative burst, and cytokine production were assessed.
- Mitochondrial membrane potential and cellular ATP levels were measured.
Main Results:
- Propofol at 3 and 30 microm did not impact cell viability, but 300 microm induced toxicity.
- Clinically relevant propofol concentrations (30 microm) suppressed macrophage chemotactic and oxidative abilities.
- Propofol reduced phagocytic activity and blocked interferon-gamma mRNA production.
- Mitochondrial membrane potential and ATP levels were decreased by propofol in a concentration-dependent manner.
Conclusions:
- Clinically relevant concentrations of propofol suppress macrophage functions.
- The mechanism involves inhibition of mitochondrial membrane potential and ATP synthesis.
- Propofol's immunosuppressive effects are not primarily due to direct cellular toxicity at therapeutic levels.