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Updated: Jun 10, 2026

Bone Marrow-derived Macrophage Production
Published on: November 22, 2013
ß-adrenergic stimulation increases macrophage CD14 expression and E. coli phagocytosis through PKA signaling
Kuzhali Muthu1, Li-K He, Andrea Szilagyi
1Department of Surgery, Loyola University Medical Center, Maywood, IL 60153, USA. kmuthu@lumc.edu
Abstract:
CD14 is a glycoprotein that binds bacterial LPS in MØ. It is an essential component of the phagocytic system and is increased in septic shock. Critical injury and sepsis result in elevated endogenous CA levels. CAs have a significant impact on MØ inflammatory functions. We tested the hypothesis that β-adrenergic stimulation regulates CD14 expression and bacterial phagocytosis in BMØ. Murine BMØ stimulated with isoproterenol (>8 h) induced a dose-dependent increase in cell surface CD14 expression. Specific PKA inhibitor (H-89) and gene-silencing (siRNA) studies demonstrated the role of cAMP-dependent PKA in mediating this response. In addition, we observed a correlation between an isoproterenol-mediated increase in CD14 expression and live Escherichia coli uptake in BMØ. Further, the essential role of CD14 in an isoproterenol-mediated increase in E. coli uptake was highlighted from experiments using CD14(-/-) mice. Moreover, the dose response of isoproterenol stimulation to CD14 expression and E. coli phagocytosis overlapped with similar EC50. Additionally, isoproterenol-mediated E. coli phagocytosis was prevented by H-89, suggesting that β-adrenergic stimulus in BMØ increases CD14 expression and live E. coli phagocytosis through a common signaling pathway. Our studies indicate the potential impact of β-adrenergic agents on important innate immune functions.
Insights
Beta-adrenergic stimulation, like with isoproterenol, boosts CD14 expression and bacterial phagocytosis in mouse bone marrow macrophages (BMØ). This pathway involves cAMP-dependent PKA, highlighting potential therapeutic roles for beta-adrenergic agents in innate immunity.
Area of Science:
- Immunology
- Cell Biology
- Pharmacology
Background:
- CD14 glycoprotein binds bacterial lipopolysaccharide (LPS) in macrophages (MØ), crucial for innate immunity.
- Elevated catecholamine (CA) levels during critical injury and sepsis impact MØ inflammatory functions.
- The role of beta-adrenergic stimulation on CD14 expression and phagocytosis in MØ remains unclear.
Purpose of the Study:
- To investigate the hypothesis that beta-adrenergic stimulation regulates CD14 expression and bacterial phagocytosis in mouse bone marrow macrophages (BMØ).
Main Methods:
- Murine BMØ were stimulated with isoproterenol.
- Inhibitor studies using H-89 (PKA inhibitor) and gene-silencing (siRNA) were performed.
- Bacterial phagocytosis was assessed using live Escherichia coli uptake.
- Experiments utilized CD14-deficient (CD14(-/-)) mice.
Main Results:
- Isoproterenol induced a dose-dependent increase in cell surface CD14 expression in BMØ.
- The response was mediated by cAMP-dependent protein kinase A (PKA).
- Increased CD14 expression correlated with enhanced E. coli uptake, dependent on CD14.
- Isoproterenol-mediated phagocytosis and CD14 expression shared similar EC50 values.
Conclusions:
- Beta-adrenergic stimulation significantly increases CD14 expression and bacterial phagocytosis in BMØ.
- This effect is mediated by a common signaling pathway involving cAMP-dependent PKA.
- Beta-adrenergic agents may represent a potential therapeutic strategy to modulate innate immune functions.
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